A potential role for α-actinin in inside-out αIIbβ3 signaling
PMID: 20940419
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: No proband or variant information; however, there is potential experimental assay information
A potential role for α-actinin in inside-out αIIbβ3 signaling
PMID: 20940419
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: No proband or variant information; however, there is potential experimental assay information
10
Case9: No assertion made on age, gender or ethnicity
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: The identified variants were heterozygote in parents.
CasePresentingHPOs: HP:0005542
(Prolonged clotting time)
CaseHPOFreeText: Bleeding time greater than 20 minutes and hematocrit of 38.1%
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: N/A
CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1392A>G (p.Pro464Pro)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA500273575
gnomAD: https://gnomad.broadinstitute.org/variant/17-42458248-T-C
9
Case9: No assertion made on age, gender or ethnicity
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: The identified variants were heterozygote in parents.
CasePresentingHPOs: HP:0000978, HP:0000132, HP:0000421,HP:0000979
(Easy bruising, menorrhagia, epistaxis, purpura)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.189_236del (c.189-319_236del)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940231
gnomAD: N/A
12
Case12: No assertion made on age, gender or ethnicity
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: The identified variants were heterozygote in parents.
CasePresentingHPOs: HP:0005542
(Prolonged clotting time)
CaseHPOFreeText: Bleeding time greater than 20 minutes, Hematocrit of 39.6%
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
CasePreviousTesting: Genetic study of patient was conducted using direct sequencing of entire coding and exon-intron boundaries of the ITGA2B and ITGB3 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.842C>T (p.Thr281Ile)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805055
gnomAD: N/A
Inherited traits affecting platelet function
PMID: 18180086
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article gives background information on GT; there is no mention of GT probands with variants in ITGA2B and/or ITGB3
RL
Case4: Patient RL
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs:
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: N/A
CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
DC
Case8: Patient DC
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs:
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: N/A
CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study
Gene: ITGA2B
Variant: NM_000419.3:c.483C>G (p.Cys161Trp)
LegacyVariant: (p.Cys130Trp)
ClinVar: N/A
CAiD: CA399805884
gnomAD: N/A
HLa
Case3: Patient HLa
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs:
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: N/A
CasePreviousTesting: The amplification of DNA fragments using PCR and their electrophoretic migration through a denaturing gradient was used to scan the entire coding region, splice site junctions and promoter regions of the GPIIb and GPIIIa genes for all 20 patients in this study
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
Successful management of perioperative hemostasis in a patient with Glanzmann thrombasthenia who underwent a right total mastectomy
PMID: 27696190
Gene: ITGA2B
HGNC: 6138
Inhibition of Platelet Aggregation byAbciximab but Not by Aspirin Can BeDetected by a New Point-of-Care Test, the Hemostatus
PMID: 10418797
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient; however, there is no mention of variants in ITGA2B and/or ITGB3; therefore, there is insufficient evidence
PreviouslyPublished: The GT patient in this article has been previously published in this PMID: 2180491
1CabGT-1
Case1: (Proband CabGT-1) Male, age not specified, China
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: Surface expression detected by flow cytometry showed <5% GPIIb and <5% GPIIIa
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: NM_000419.3:c.531T>A (p.Cys177Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290955739
gnomAD N/A
7CabGT-7
Case7: (Proband CabGT-7) Female, age not specified, Caucasian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: Flow cytometry showed <5% GPIIb and 11% GPIIIa surface expression
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: The first variant was found to be: NM_000419.3:c.1563T>A (p.Cys521Ter) and they did not find the second mutation
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290950094
gnomAD N/A
3CabGT-3
Case3: (Proband CabGT-3), Male, age not specified, European Caucasian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: N/A
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and c.1442-13_1442-1del, which is not showing up in CAR (Unregistered Variant?)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290950815 (p.Ile405Thr)
gnomAD N/A
9CabGT-9
Case9: (Proband CabGT-9), Female, age not specified, Kuwait
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: N/A
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: NM_000419.3:c.1879-2A>G
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290949031
gnomAD N/A
17CabGT-17
Case17: (Proband CabGT-17), Male, age not specified, North African
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: Flow cytometry showed 13% GPIIb and 27% GPIIIa surface expression
Platelet Aggregation: N/A
CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence
Gene: ITGA2B
Variant: NM_000419.3:c.2929C>T (p.Arg977Ter) and the other mutation could not be found
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8602528
gnomAD MAF in the South Asian population is 0.00003266 https://gnomad.broadinstitute.org/variant/17-42452041-G-A
aIIbb3 Integrin: New Allelic Variants in GlanzmannThrombasthenia, Effects onITGA2BandITGB3mRNASplicing, Expression, and Structure–Function
PMID: 20020534
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
Recombinant factor VIIa enhances deposition of platelets with congenital or acquired αIIbβ3 deficiency to endothelial cell matrix and collagen under conditions of flow via tissue factor–independent thrombin generation
PMID: 12411291
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT probands with variants in ITGA2B and/or ITGB3 therefore there is no evdience; however, there may be potenetial experimental assay information
Interactionofhumanplateletswithlamininandidentificationofthe67kDalamininreceptoronplatelets
PMID: 1826081
Gene: ITGA2B and ITGB3 (we are noting these gene names even though there is no evidence for GT in this article, because we are curating for these genes-- CThaxton advised it would be a good idea to always note down Genes and HGNC)
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report. The studies performed in this article were undertaken to characterize the interaction of platelets with laminin.
M/10
Case2: Male, 10 years old, Andra Pradesh India
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0031364, HP:0002239, HP:0000225
(Epistaxis, ecchymosis, GI bleeding, gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1 for values
PlateletAggregation: See Table 1 for values
CasePreviousTesting: PCR amplification of ITAG2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.475G>A (p.Gly159Ser)
LegacyVariant: (p.Gly128Ser)
ClinVar: N/A
CAiD: CA8603454
gnomAD: MAF in the South Asian population is 0.00003267 https://gnomad.broadinstitute.org/variant/17-42463018-C-T
M/13
Case1: Male, 13 years old, Andra Pradesh India
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0006298, HP:0000421, HP:0000967, HP:0002239, HP:0000225
(Prolonged bleeding after dental extraction, epistaxis, petechiae, GI bleeding, gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1 for values
PlateletAggregation: See Table 1 for values
CasePreviousTesting: PCR amplification of ITAG2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.48G>A (p.Trp16Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399807046
gnomAD: N/A
F/28
Case5: Female, 28 years old, Goa India
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0031364, HP:0002239, HP:0000225, HP:0006298, HP:0000967, HP:0000132
(Ecchymosis, GI bleeding, gingival bleeding, prolonged bleeding after tooth extraction, petechiae, menorrhagia)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1 for values
PlateletAggregation: See Table 1 for values
CasePreviousTesting: PCR amplification of ITAG2B and ITGB3
Gene: ITGA2B
Variant: IVS15-1 G>A can't be found in the allele registry by me I am noting it as Unreg
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8603039
gnomAD: N/A
Are bone defects in rare patients with Glanzmann’s thrombastheniaassociated withITGB3orITGA2Bmutations?
PMID: 21557682
Gene: ITGA2B
HGNC: 6138
Successful Management of Acute Catastrophic Juvenile Vaginal Bleeding in Glanzmann's Thromboasthenia by Uterine Tamponade: A Case Report and Review of The Literature
PMID: 22928124
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article reports a case of acute catastrophic vaginal bleeding in a girl, who was diagnosed with GT and responded to uterine tamponade for acute control of vaginal bleeding; however, no variants in ITGA2B and/or ITGB3 are mentioned in this article therefore we have insufficient evidence
The French patient who is the object of this study is now an elderly male with a lifelong but mild bleeding disorder
Case1: Male, French, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A "Has no surviving close relatives"
ParentalGenotype:
CasePresentingHPOs: HP:0002239 (GI bleeding)
CaseHPOFreeText: Hemorrhage
CaseNotHPOs: HP:0000421, HP:0000225
(Epistaxis, gingival bleeding)
CaseNotHPOsFreeText: N/A
ProteinExpression:
PlateletAggregation: Total lack of platelet aggregation in response to physiologic agonists and also defective clot retraction
CasePreviousTesting: Direct sequencing of all exons and splice sites of ITGA2B was performed and sequencing of the 15 exons, splice sites, and promoter of ITGB3 was also performed
Gene: ITGA2B
Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and NM_000419.3:c.1882C>T (p.Arg628Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290950376 and CA399801310
gnomAD: MAF in European (non-Finnish) population 0.000008791 http://gnomad.broadinstitute.org/variant/17-42457994-G-C and MAF in the Latino population is 0.00003983 http://gnomad.broadinstitute.org/variant/17-42456075-G-A
FLOW CYTOMETRIC ANALYSIS OF PLATELET SURFACE GLYCOPROTEINS IN THE DIAGNOSIS OF BERNARD-SOULIER SYNDROME
PMID: 9021812
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report
Supplementary Table S1:
Case23: GT26, French, gender and age not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1073G>A (p.Arg358His)
LegacyVariant: N/A
ClinVar: 2896
CAiD: CA115839
gnomAD: N/A
Supplementary Table S1:
Case10: GT11, French/German, age and gender not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1073G>A (p.Arg385His) NM_000419.3:c.1234G>A (p.Gly412Arg)
LegacyVariant: N/A
ClinVar: 2896 and 381748
CAiD: CA115839 and CA8603182
gnomAD: MAF in the Latino population for (p.Gly412Arg) is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T
Supplementary Table S1:
Case65: GT76, French, gender and age are not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.2421G>A (p.Trp807Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399796017
gnomAD: N/A
Supplementary Table S1:
Case15: GT18, French, gender and age not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1201G>T (p.Gly401Cys) and NM_000419.3:c.2800G>T (p.Val934Phe)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399804280 and CA290946484
gnomAD: N/A
Supplementary Table S1:
Case27: GT31, "USA"- what the supp table stated, gender and age are not specified here at this time
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1771dup (p.Asp591Glyfs*47) and NM_000419.3:c.3061-1G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940334 and CA399787972
gnomAD: N/A
Supplementary Table S1:
Case63: GT74, French, gender and age are not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients had a life-long history of mucocutaneous bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: All patients in this study met the clinical and platelet function requirements for GT-- this includes an absent or strongly reduced expression of alphaIIbBeta3 in platelets
PlateletAggregation: All patients in this study met the clinical and platelet function requirements for GT-- this includes absent or severely reduced platelet aggregation with at least three physiological agonists
CasePreviousTesting: Sanger sequencing was performed. Sanger sequencing ensured coverage of all exons and splice sties of the ITGA2B and ITGB3 genes and extended 300-500 bp into the introns as well as including the UTR. They sequenced 416 bp upstream of the ITGA2B promoter and 463 bp upstream of the ITGB3 promoter. In total they sequenced 51.2% of the ITGA2B gene and 19.4% of the larger ITGB3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.1440-13_1440-1del (p.Arg480SerfsTer106)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290950815 and CA913184940
gnomAD: N/A
VISUALIZATION OF PLATELET GLYCOPROTEINS Ib AND IIIa BY IMMUNOENZYMATIC STAIN USING AVIDIN-BIOTIN PEROXIDASE COMPLE
PMID: 1788826
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence
M8
Case16: (M8) Male, 47 years old, French Gypsy
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Mucocutaneous bleeding
CaseNotHPOs: N/A
ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets
Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)
CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD N/A
M15
Case13: (M15) Female, 42 years old, French Gypsy
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Mucocutaneous bleeding
CaseNotHPOs: N/A
ProteinExpression: Failed to express alphaIIbbeta3 on the surface of their platelets
Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)
CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD N/A
GT5
Case5: (GT5) Female, 55 years old, French
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Mucocutaneous bleeding
CaseNotHPOs: N/A
ProteinExpression: <5% surface expression levels of αIIbβ3
Platelet Aggregation: Absent platelet aggregation to all agonists (no mention for which agonists or response to ristocetin)
CasePreviousTesting: All the information we are given is "mutation screening of the ITGA2B and ITGB3 genes" the method for sequencing etc. was not stated
Gene: ITGA2B
Variant: NM_000419.3:c.1063G>A (p.Glu355Lys)
LegacyVariant: (p.Glu324Lys) (The paper gives legacy and current nomenclature)
ClinVar: 2899
CAiD: CA115844
gnomAD MAF in the European (non-Finnish) population is 0.00001978 https://gnomad.broadinstitute.org/variant/17-42461008-C-T
c.621C>T, homozygous).26
based on the reference provided this is likely supposed to be c.620C>T (p.Thr207Ile) and the patient has already been reported and scored in the curation
Platelet Glycoprotein IIb/IIIa Receptors and Glanzmann’s Thrombasthenia Deborah L. French and Uri SeligsohnFrom the Mount Sinai School of Medicine (D.L.F.), New York, NY, and The Chaim Sheba Medical Center (U.S.), Tel-Hashomer, Israel.
PMID: 10712380
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This review mentions many variants in ITGA2B and ITGB3; however, there are no probands to tie these variants to therefore there is insufficient evidence
Supplementary Tables 1 and 2 combined information:
Case20a: GT20a, Male, 30 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Family information available in Table1 (brother of GT20b)
ParentalGenotype: Parents are consanguineous, no other genotype information available
CasePresentingHPOs: HP:0000225
(Gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
Gene: ITGA2B
Variant: NM_000419.3:c.1882C>T (p.Arg628Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399801310
gnomAD: MAF in Latino population: 0.00003983 https://gnomad.broadinstitute.org/variant/17-42456075-G-A
Supplementary Tables 1 and 2 combined information:
Case16: GT16, Male, 31 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Available per supplementary table 1; however very minimal information
ParentalGenotype: Parents are not consanguineous, no other genotype information available
CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000421, HP:0000225
(Bruising, purpura, ecchymosis, epistaxis, gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
Gene: ITGA2B
Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.2267+1G>T no protein coding sequence available
LegacyVariant: N/A
ClinVar: 225393 (p.Gln778Pro)
CAiD: CA290947544 (p.Gln778Pro) and CA399798124 for (c.2267+1G>T )
gnomAD: N/A
Supplementary Tables 1 and 2 combined information:
Case32: GT32, Male, 9 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Not available per supplementary table 1
ParentalGenotype: Parents are not consanguineous, no other genotype information available
CasePresentingHPOs:HP:0000421
(Epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Showed 10-20% of αIIbβ3 expression measured by flow cytometry
PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
Gene: ITGA2B
Variant: NM_000419.3:c.886G>A (p.Gly296Arg) and NM_000419.3:c.460_462del (p.Glu154del)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8603306 (p.Gly296Arg) and CA8603457 (p.Glu154del)
gnomAD: MAF in East Asian population: 0.00005454 https://gnomad.broadinstitute.org/variant/17-42461684-C-T and MAF in European (non-Finnish) population 0.000008870 https://gnomad.broadinstitute.org/variant/17-42463030-TCTC-T
Supplementary Tables 1 and 2 combined information:
Case9: GT9, Female, 25 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Not available per supplementary table 1
ParentalGenotype: Parents are consanguineous, no other genotype information available
CasePresentingHPOs: HP:0000421, HP:0000132
(Epistaxis, menorrhagia)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Showed <5% of αIIbβ3 expression measured by flow cytometry
PlateletAggregation: Platelet aggregation showed no response to ADP and collagen but normal response to ristocetin
CasePreviousTesting: All exons from ITGA2B and ITGB3 genes were amplified by PCR using intronic primers. DNA sequencing was determined by Sanger sequencing.
Gene: ITGA2B
Variant: NM_000419.3:c.2333A>C (p.Gln778Pro)
LegacyVariant: N/A
ClinVar: 225393
CAiD: CA290947544
gnomAD: N/A
Clinical And Molecular Insights into Glanzmann’s Thrombasthenia in China
PMID: 29675921
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156, respectively as gene names shown above
Supplementary Table S1 & S2 Proband and Variant Information:
Case9: GT10, Male, 45, French and Italian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Mild lifelong bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed 30-50% variant expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Residual platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.3077G>A (p.Arg1026Gln)
LegacyVariant: N/A
ClinVar: 50232
CAiD: CA913184940 and CA10575572
gnomAD: MAF in the European (non-Finnish) population 0.00006482 http://gnomad.broadinstitute.org/variant/17-45363676-T-C and MAF in the European (non-Finnish) population is 0.000008801 http://gnomad.broadinstitute.org/variant/17-42449775-C-T
Supplementary Table S1 & S2 Proband and Variant Information:
Case10: GT11, Female, 54, French and German
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132
(Epistaxis, gingival bleeding, menorrhagia)
CaseHPOFreeText: Spontaneous bruising
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed 10-15% variant expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)
LegacyVariant: N/A
ClinVar: 2896 and 381748
CAiD: CA115839 and CA8603182
gnomAD: MAF in the Latino population is 0.0001453 http://gnomad.broadinstitute.org/variant/17-42458406-C-T
Supplementary Table S1 & S2 Proband and Variant Information:
Case70: GT74, Female, 14 years old, French
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0002239, HP:0002249
(GI bleeding, melena)
CaseHPOFreeText: Serious mouth bleeding, post traumatic heavy bruising, heavy bleeding after adenoid removal
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed less than 5% αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.1440-13_1440-1del (p.Arg480Serfs*106)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290950815 and CA913184940
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case30: GT34, Male, 15 years old, US
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0002239
(Epistaxis, GI bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1553T>A (p.Ile518Asn) and NM_000419.3:c.1946+3G>T
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8603038 and CA626121071
gnomAD: MAF in the European (non-Finnish) is 0.000008790 http://gnomad.broadinstitute.org/variant/17-42457661-A-T and MAF in the African population is 0.000 http://gnomad.broadinstitute.org/variant/17-42456008-C-A
Supplementary Table S1 & S2 Proband and Variant Information:
Case25: GT28, Male, 36, French/Syrian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Affected sister (See Supplemental Table 1)
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: "LR Dup" (See Supplementary Table 1)
LegacyVariant: N/A
ClinVar: N/A
CAiD: N/A
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case34: GT36b, Male, 60 years old, Spanish
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Affected sisters who are proband 36a and 36c in this study
ParentalGenotype: N/A
CasePresentingHPOs: HP:0004406
(Recurrent epistaxis)
CaseHPOFreeText: Embolism of the submaxillary artery
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.131G>T (p.Gly44Val) and NM_000419.3:c.1440-13_1440-1de (p.Arg480Serfs*106)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399806881 and CA913184940
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case66: GT69, Female, 32 years old, French
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978, HP:0000979, HP:0004406, HP:0000132, HP:0004846
(Bruising, purpura, recurrent epistaxis, menorrhagia, prolonged bleeding after surgery)
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0006298 (Prolonged bleeding after dental extraction)
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1878G>C (p.Gln626His)
LegacyVariant: N/A
ClinVar: 2903
CAiD: CA115852
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case16: GT19, Female, 44, French (Gypsy)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Brother and cousin are other affected family members (This is all the information we are given, see Supplementary Table 1)
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978, HP:0000132, HP:0000421, HP:0000225
(Easy bruising, menorrhagia, epistaxis, gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A (p.Val513Leufs*71)
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
Supplementary Table S1 & S2 Proband and Variant Information:
Case24: GT27, Female, 84 at death, French
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0031364, HP:0002239
(Ecchymosis, GI bleeding)
CaseHPOFreeText: Bleeding following trauma
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed 5-10% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.1413C>G (p.Tyr471Ter) and NM_000419.3:c.2468G>A (p.Gly823Glu)
LegacyVariant: N/A
ClinVar:
CAiD: CA290950376 and CA399795351
gnomAD: MAF in the European (non-Finnish) population 0.000008791 http://gnomad.broadinstitute.org/variant/17-42457994-G-C MAF in African population is 0.000 http://gnomad.broadinstitute.org/variant/17-42453334-C-T
Supplementary Table S1 & S2 Proband and Variant Information:
Case61: GT64, Female, 26 years old, French
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0000978, HP:0000132, HP:0000225, HP:0031364
(Epistaxis, easy bruising, menorrhagia, gingival bleeding, ecchymosis)
CaseHPOFreeText: Mouth and tonsil bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3 (See Supplementary Table 1)
PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)
CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3
Gene: ITGA2B
Variant: NM_000419.3:c.257T>C (p.Leu86Pro) and NM_000419.3:c.1440-13_1440-1del
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290956162 and CA913184940
gnomAD: N/A
Supplemental Table S1:
Cases6-11: Males and Females from India/Pakistan, ages not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Moderate to severe bleeding tendency in these patients
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: NM_000419.3:c.1652G>A (p.Arg551Gln)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8602986
gnomAD: MAF in the South Asian population is 0.00006536 https://gnomad.broadinstitute.org/variant/17-42457470-C-T
PreviouslyPublished: PMID: 19172520 and 26896847
Supplemental Table S1:
Cases 13-18: Males and Females, from Sweden, France and Germany and other places, ages are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Moderate to severe bleeding when data was available
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: 5%/<5% when homozygous αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: NM_000419.3:c.1787T>C (p.Ile596Thr)
LegacyVariant: N/A
ClinVar: 2900
CAiD: CA115846
gnomAD: MAF in the European non finnish pop is 0.0001325 https://gnomad.broadinstitute.org/variant/17-42457148-A-G
PreviouslyPublished: PMID: 9215749, 9734640, 20020534, 22513797, 25373348
Supplemental Table S1:
Cases19-23: Males and Females from France, North Africa, Italy and Germany, ages are not specified for these patients
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: NM_000419.3:c.1878G>T (p.Gln626His)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399801470
gnomAD: N/A
PreviouslyPublished: PMID: 21113249, 20020534, 22513797, 25728920
Supplemental Table S1:
Case24: N/A (from Turkey)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: Individual clinical data not given
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: Thr646Ala* (Need to consult senior biocurator to figure this variant out) will note it as Unknown as I am not sure of it
LegacyVariant: ^
ClinVar: ^
CAiD: ^
gnomAD: ^
PreviouslyPublished: PMID: 25734216
Supplemental Table S1:
Cases35and36: Females, USA, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Severe bleeding
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <5% αIIbβ3 expression
PlateletAggregation: Absent platelet aggregation (all the information that is provided in Supp. Table S1)
CasePreviousTesting: Sanger sequencing of exons, splice sites and untranslated regions of the ITGA2B and ITGB3 genes was performed
Gene: ITGA2B
Variant: NM_000419.3:c.2264G>A (p.Arg755Gln)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8602771
gnomAD: MAF in the Latino population is 0.0001903 https://gnomad.broadinstitute.org/variant/17-42454380-C-T
PreviouslyPublished: PMID: 25728920
B
Case2: Patient ID B, Male, 16 years old, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Table 1 asserts family information is provided; however, minimal information
ParentalGenotype: N/A
CasePresentingHPOs: HP:0004406, HP:0000225
(Recurrent epsitaxis, gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin
CasePreviousTesting: Exon PCR was used to amplify a;; coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.
Gene: ITGA2B
Variant: NM_000419.3:c.641T>G (p.Leu214Arg)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805518
gnomAD: MAF in South Asian population 0.00003266 http://gnomad.broadinstitute.org/variant/17-42462561-A-C
H
Case8: Patient ID H, Female, 8 years old, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A (Table 1 does mention family history of bleeding)
ParentalGenotype: N/A (Parents are consangenous)
CasePresentingHPOs: HP:0000978, HP:0004406, HP:0000225, HP:0002239, HP:0005261
(Easy bruising, recurrent epistaxis, gingival bleeding, GI bleeding, hemarthrosis)
CaseHPOFreeText: Hemorrhage after dental, hemorrhage after trauma, ear bleeding
CaseNotHPOs: HP:0000967, HP:0000979, HP:0002239, HP:0000790, HP:0002248
(Petechiae, purpura, intracranial hemorrhage, hematuria, hematemesis)
CaseNotHPOsFreeText: Hematoma
ProteinExpression: N/A
PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin
CasePreviousTesting: Exon PCR was used to amplify a;; coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.
Gene: ITGA2B
Variant: NM_000419.3:c.1652G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA8602986
gnomAD: MAF in South Asian population is 0.00006536 http://gnomad.broadinstitute.org/variant/17-42457470-C-T
PreviouslyPublished: PMID: 19172520
D
Case4: Patient ID D, Male, 10 years old, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Related to Patient C
ParentalGenotype: N/A
CasePresentingHPOs: HP:0004406 (Recurrent epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: HP:0000967, HP:0000979, HP:0000978, HP:0000225, HP:0002239, HP:0002239, HP:0000790, HP:0005261, HP:0002248
(Petechiae, purpura, easy bruising, gingival bleeidng, GI bleeding, intracranial hemhorrage, hematuria, hemarthrosis, hematemesis)
CaseNotHPOsFreeText: Hemorrhage after dental, hemorrhage after trauma, ear bleeding, hematoma
ProteinExpression: N/A
PlateletAggregation: Defective response to ADP, adrenaline, collagen, arachidonic acid, and normal response to ristocetin
CasePreviousTesting: Exon PCR was used to amplify a;; coding regions of the ITGA2B and ITGB3 genes. PCR products were purified and Sanger sequenced. Segregation using parental samples was undertaken when available.
Gene: ITGA2B
Variant: NM_000419.3:c.1233C>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399803781
gnomAD: N/A
PreviouslyPublished: PMID: 12424194
40-year-old woman
Case#: 40 yo, Female, W. Turkey
DiseaseAssertion: Glanzmann Thrombasthenia
FamilyInfo: Consanguineous (cousins).
ParentalGenotype: Both carriers.
CasePresentingHPOs: (HP:0007420) Spontaneous hematomas, (HP:0001892) Abnormal bleeding, (HP:0100608) Metrorrhagia, (HP:0001935) Microcytic anemia, (HP:0034263) Abnormal vaginal bleeding, (HP:0004944) Cerebral aneurysm,
PlateletAggregation: Hypochromic anemia and a platelet count of 198 × 109/L (normal range 150–400 × 109/L). Platelet aggregometry showed no aggregation after stimulation with collagen (2 and 10 µg/mL), ADP (4 and 10 µmol/L), and epinephrine (8 µmol/L) (norm > 70%), and reduced (42%, Norm > 70%) agglutination after stimulation with ristocetin (1.2 mg/mL).
CaseHPOFreeText: Received platelet concentrates multiple times as a young adult before dental surgery. Pregnancy, alloantibodies to glycoprotein αIIbβ3 were detected in the patient’s blood. emergency caesarean section was performed in another hospital. Because the patient developed severe bleeding problems, she received two red cell units, two pooled platelet concentrates, tranexamic acid, and desmopressin intraoperatively. Two drainages were placed. Three platelet concentrates were transfused in the following days, resulting in a first-time transfusion reaction. Emergency cesarean- endometrial coagulation, operative hysteroscopy.
ProteinExpression: Flow cytometry showed the absence of expression of CD41 (integrin αIIbβ3) and severely impaired fibrinogen binding after ADP activation
CasePreviousTesting: molecular genetic analysis was performed using a custom gene panel for inherited platelet disorders (Nextera Rapid Custom Enrichment, Illumina, San Diego, CA, USA) established in our department, followed by sequencing on a MiSeq (Illumina)
Gene: ITGA2B
HGVS: 6138
ClinVar: Unregistered
CAID: CA2261369696
gnomAD: Absent
Gene: ITGA2B
HGVS: 6138
ClinVar: Unregistered
CAID: CA2261369696
gnomAD: Absent
Management challenge of a rare concomitant platelet glycoprotein IV/CD36 and IIb/IIIa deficiencies: Case illustration
PMID: 40033798
Gene: ITGA2B
GNC: 6138
Double heterozygosity of the GPIIb gene in a Swiss patient with Glanzmann's thrombasthenia
PMID: 9734640
Gene: ITGA2B
HGNC: 6138
1
Case1: Male, 3.5 years old, Indian
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: (HP:0000421 Epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: Diagnosis of GT was made on the basis of quantitive determination of receptor count by flow cytometric analysis of GPIIb-IIIa
PlateletAggregation: Diagnosis of GT was made on the basis of impaired platelet aggregation (platelet aggregation was tested against ristocetin, ADP, collagen, epinephrine and arachidonic acid)
CasePreviousTesting: Multiplex PCR by using GPIIb primers and CSGE analysis were performed
Gene: ITGA2B
Variant: NM_000419.3:c.1286G>A (p.Asp396Asn)
LegacyVariant: (p.Asp365Asn)
ClinVar: N/A
CAiD: CA399803675
gnomAD: N/A
Case 1
Case#: Case 1, 35 yo Female
DiseaseAssertion: Glanzmann thrombasthenia
ParentalGenotype: Not provided
CasePresentingHPOs: (HP:0031364, Ecchymosis) (HP:0034000, Tracheal hemorrhage)
PlateletAggregation: Responded partially to tranexamic acid
CaseHPOFreeText: intrauterine blood clots
CaseNotHPOs:
CaseNotHPOFreeText:
ProteinExpression: Western blot, trace amounts of αIIb and residual expression of β3
CasePreviousTesting: Molecular analysis
PreviouslyPublished: Not provided
Gene: ITGA2B
HGVS: NM_000419.5:c.2095-19T>A
ClinVar: 1691455 https://www.ncbi.nlm.nih.gov/clinvar/variation/1691455/
CAID: CA915940312
gnomAD: Absent
Gene: ITGA2B
HGVS: NM_000419.5:c.2770C>T
ClinVar: 1691475 https://www.ncbi.nlm.nih.gov/clinvar/variation/1691475/
CAID: CA399792054
gnomAD: PopMax = 0.000002616 https://gnomad.broadinstitute.org/variant/17-44375069-G-A?dataset=gnomad_r4
The GPIIb/IIIa (integrin αIIbβ3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend
PMID: 18840725
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article is a review discussing the integrin αIIbβ3, there is no mention of probands with variants in ITGA2B and/or ITGB3
Inherited bleeding disorders: disorders of plateletadhesion and aggregation
PMID: 9351872
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article is a review on GT
GT-63
Case51: (GT-63) Female, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Severe (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.558C>G (p.Tyr186Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805728
gnomAD: N/A
GT-48
Case38: (GT-48) Male, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Proband GT45-GT48 are related
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Moderate (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1879-2A>G
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290949031
gnomAD: N/A
GT-09
Case8: (GT-09) Male, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Probands 1-8 are related to GT-09 see Table 1
ParentalGenotype: Parents may be included in Table 1; however, not specified so no information
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Information not available (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry results not available (See Supplemental Table 3)
PlateletAggregation: No information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1210+5G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940251
gnomAD: N/A
GT-01
Case1: (GT-01) Male, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type 1
FamilyInfo: Probands 2-9 are related to GT-01 see Table 1
ParentalGenotype: Parents may be included in Table 1; however, not specified so no information
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Severe (See Supplemental Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 not observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1210+5G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940251
gnomAD: N/A
GT-37
Case32: (GT-37) Female, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Proband GT31-GT34 are related
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Severe (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1879-2A>G
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290949031
gnomAD: N/A
Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients
PMID: 30792900
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156 respectively as shown above
GT-26
Case22: (GT-26) Male, age or ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Proband GT-26 is related to GT-25 see Table 1
ParentalGenotype: Parents may be included in Table 1; however, not specified so no information
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding severity: Severe (See Supplementary Table 3)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry performed and CD41 and CD61 were observed (See Supplementary Table 3)
PlateletAggregation: Minimal information (See Supplementary Table 3)
CasePreviousTesting: DNA was extracted from peripheral blood samples from patients and family members, and Sanger sequencing and PCR was performed. Samples were processed for targeted sequencing using the available SHGp heme panel of 393 genes.
Gene: ITGA2B
Variant: NM_000419.3:c.1879-2A>G
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290949031
gnomAD: N/A
A simple, novel and robust test to diagnose type I Glanzmann thrombasthenia
PMID: 18450741
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InusufficientEvidence: This article used a bifunctional bioengineered disintegrin/alkaline phosphatase hybrid protein ErAPv to evaluate 14 consecutive cases of Glanzmann thrombasthenia and 20 normal healthy controls. Thererefore, GT probands are mentioned; however, no specific variants in ITGA2B and/or ITBG3 have been mentioned in these patients
A Rare Case of Bleeding Disorder: Glanzmann's Thrombasthenia
PMID: 29063905
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case of an individual with Glanzmann thrombasthenia; however, no specific variants mentioned in proband.
TA
Case12: Patient TA, gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: His son is Patient TE
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 6
PlateletAggregation: See Table 6
CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries
Gene: ITGA2B and ITGB3
Variant: ITGA2B variant: NM_000419.3:c.3060G>A and ITGB3 variant: NM_000212.2:c.856G>A (p.Gly286Arg)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA500261104 and CA400020688
gnomAD: MAF in the European (non-Finnish) population is 0.00001760 https://gnomad.broadinstitute.org/variant/17-45364514-G-A for the ITGB3 variant
OK
Case1: Patient OK, gender, age, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 6
PlateletAggregation: See Table 6
CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries
Gene: ITGA2B
Variant: NM_000419.3:c.620C>T (p.T207I)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805570
gnomAD: N/A
MM
Case2: Patient MM, gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 6
PlateletAggregation: See Table 6
CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries
Gene: ITGA2B
Variant: NM_000419.3:c.641T>C (p.Leu214Pro)
LegacyVariant: N/A
ClinVar: 2901
CAiD: CA115848
gnomAD: N/A
Novel Mutations in the GPIIb and GPIIIa Genes in Glanzmann Thrombasthenia
PMID: 21113249
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
LN
Case16: Patient LN, gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: Parents are heterozygous for mutation (LH and LB)
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 6
PlateletAggregation: See Table 6
CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries
Gene: ITGA2B
Variant: NM_000419.3:c.3062T>C
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399787956
gnomAD: N/A
Patientstudies.
Case1: Female, 14 years old, German
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978 (Bruising)
CaseHPOFreeText: Severe hemorrhage after tonsillectomy, bleeding after shedding off her deciduous teeth, prolonged cutaneous bleeding time > 20 minutes
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: Flow cytometry revealed that the proband expressed only 7-10% of GPIIb-IIIa on the platelet surface
PlateletAggregation: Absent aggregation in response to ADP, collagen, epinephrine, and arachidonic acid but normal platelet aggregation in response to ristocetin
CasePreviousTesting: Sequence analysis of PCR amplifeid platelet GPIIb mRNA was performed
Gene: ITGA2B
Variant: NM_000419.3:c.1073G>A (p.Arg358His)
LegacyVariant: (p.Arg327His)
ClinVar: 2896
CAiD: CA115839
gnomAD: N/A
M4
Case4: Patient M4, Male, French Gypsy, age is not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: See Figure 2 for pedigree It shows this patient is unaffected
ParentalGenotype: Unaffected parents see pedigree Fig 2
CasePresentingHPOs: N/A
CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)
PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
M8
Case8: Patient M8, Male, French Gypsy, age is not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: See Figure 2 for pedigree
ParentalGenotype: Unaffected parents see pedigree Fig 2
CasePresentingHPOs: N/A
CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)
PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
Founder effect and estimation of the age of the French Gypsy mutation associated with Glanzmann thrombasthenia in Manouche families
PMID: 21487445
Gene: ITGA2B
HGNC: 6138
M3
Case3: Patient M3, Male, French Gypsy, age is not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: See Figure 2 for pedigree It shows this patient is unaffected
ParentalGenotype: Unaffected parents see pedigree Fig 2
CasePresentingHPOs: N/A
CaseHPOFreeText: France, GT is particularly frequent in the Gypsy population, mainly represented by the Manouche tribe. Their clinical phenotype is the same as for classic type I disease, with a moderate and occasional severe bleeding syndrome
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analysis has shown that these patients' surface expresses <5% of normal GPIIIa and GPIIb levels (we are not given an exact value for each proband)
PlateletAggregation: "Absent platelet aggregation" this is all the information we are given for platelet aggregation
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1G>A
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
Patient 2
Case2: Patient 2, Male, 4 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Affected brother is Patient 1
ParentalGenotype: Mother and father revealed heterozygosity for c.1878G>C mutation. (Parents are consanguineous)
CasePresentingHPOs: HP:0000967 (Petechiae)
CaseHPOFreeText: Hematomas, prolonged in vitro bleeding time
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analysis revealed that there was 109 of GPIIb/IIIa expression for Patient 2
PlateletAggregation: All patients' platelets showed severely reduced platelet aggregation after stimulation with collagen and ADP in contrast to the normal range (See Table 1). Stimulation with epinephrine and arachidonic acid also demonstrated decreased platelet aggregation. In contrast, ristocetin-induced platelet aggregation was borderline for Patient 2
CasePreviousTesting: Sequenced ITGA2B and ITGB3 genes from one patient of each family (Patient 2 and 3) and Patient 1 and 4 were screened for the identified mutation in the corresponding family.
Gene: ITGA2B
Variant: NM_000419.3:c.1878G>C (p.Gln626His)
LegacyVariant: N/A
ClinVar: 2903
CAiD: CA115852
gnomAD: N/A
Patient 3
Case3: Patient 3, Female, 16 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Affected sister is Patient 4
ParentalGenotype: N/A (Not consanguineous Caucasians, showed no increased bleeding tendency)
CasePresentingHPOs: HP:0000967, HP:0000225, HP:0000132
(Petechiae, gingival bleeding, menorrhagia)
CaseHPOFreeText: Hematomas, prolonged in vitro bleeding time
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analysis revealed that there was 580 of GPIIb/IIIa expression for Patient 3
PlateletAggregation: All patients' platelets showed severely reduced platelet aggregation after stimulation with collagen and ADP in contrast to the normal range (See Table 1). Stimulation with epinephrine and arachidonic acid also demonstrated decreased platelet aggregation.
CasePreviousTesting: Sequenced ITGA2B and ITGB3 genes from one patient of each family (Patient 2 and 3) and Patient 1 and 4 were screened for the identified mutation in the corresponding family.
Gene: ITGA2B
Variant: NM_000419.3:c.1787T>C (p.Ile596Thr)
LegacyVariant: N/A
ClinVar: 2900
CAiD: CA115846
gnomAD: MAF in the European (non-Finnish) population is 0.0001325 http://gnomad.broadinstitute.org/variant/17-42457148-A-G
High-level transgene expression in induced pluripotent stem cell–derived megakaryocytes: correction of Glanzmann thrombasthenia
PMID: 24335497
Gene: ITGA2B
HGNC: 6138
Human IgG Monoclonal Anti-αIIbβ3-Binding Fragments Derived from Immunized Donors Using Phage Display
PMID: 11823541
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions 1 GT proband; however, variants in ITGA2B and/or ITGB3 are not mentioned.
Iraqi-JewishandArabpopulationsinIsrael
PMID: 2014236
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article does not mention specific case reports- rather, this article mentions two different populations harboring variants. I have annotated the 2 variants each cohort harbors
Should studies on Glanzmann thrombasthenia not be telling us more about cardiovascular disease and other major illnesses?
PMID: 28395882
Gene: ITGA2B and ITGB3
HGNC: 6139 and 6156
Adult woman/Belgium
Case3: Female (adult), 48 years old, Belgium
DiseaseAssertion: Glanzmann thrombasthenia (also has cancer)
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: N/A
Platelet Aggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1772A>C (p.Asp591Ala)
LegacyVariant: (p.Asp560Ala)
ClinVar: N/A
CAiD: CA8602942
gnomAD MAF in the European (non-Finnish) population is 0.00001556 https://gnomad.broadinstitute.org/variant/17-42457163-T-G
PreviouslyPublished: PMID: 21919374
Woman/Germany
Case6: Female, age not specified, Germany
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
ProteinExpression: N/A
Platelet Aggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)
Note: This article mentions this patient as having a G391R mutation; however, this article cites this patient in citation 6; where that article states this patient has a G412R mutation. There is some typo here. I am using the information given in Reference 6. The proband is #11 in reference 6.
LegacyVariant: (p.Arg327His) (Not writing legacy for the other variant, as there is some typo between articles)
ClinVar: 2896 for the (p.Arg358His) mutation and 381748 for (p.Gly412Arg)
CAiD: CA115839 for (p.Arg358His) and CA8603182 for (p.Gly412Arg)
gnomAD MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T
GT 28
Case9: GT28, Male, India, age of onset is 5 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1139G>T (p.Gly380Val)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399804402
gnomAD: N/A
GT12
Case3: GT12, Male, India, age of onset is 13 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.2015del (p.Gly672AlafsTer22)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940724
gnomAD: N/A
GT 43
Case13: GT43, Female, India, age of onset is 18 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.1520C>G (p.Pro507Arg)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399802643
gnomAD: N/A
GT 29
Case10: GT29, Fe,a;e, India, age of onset is 3 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGA2B
Variant: There is an error in this article, they state the mutation is c.683 but really in CAR we see it is c.682 --> I have changed it: NM_000419.3:c.682C>T (p.Gln228Stop) and NM_000419.3:c.886G>A (p.Gly296Arg)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805421 and CA8603306
gnomAD: MAF in the East Asian population is 0.00005454 https://gnomad.broadinstitute.org/variant/17-42461684-C-T
GT 22
Case5: GT22, Female, India, age of onset is 34 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Patients were recruited as they presented consecutively from 1996 to 1998 for evaluation of a mucocutaneous bleeding disorder
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: All patients examined had defective ADP, epinephrine, and collagen induced aggregation and normal ristocetin induced aggregation
CasePreviousTesting: Mutations were detected by the method of single strand conformation polymorphism (SSCP) analysis, followed by nucleotide sequencing and confirmation by restriction fragment length polymorphism (RFLP) assays. The sequences of the primers employed and the reaction conditions for PCR amplification of the exons, adjacent intronic regions, and 50 and 30 untranslated regions of the aIIb and b3 gene
Gene: ITGA2B
Variant: NM_000419.3:c.416C>T (p.Ala139Val)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399806036
gnomAD: N/A
GT1
Case1: (GT1), Gender, age and ethnicity not reported
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: 1 brother and 1 sister that are both heterozygous for g.951G>A and p.Leu343Pro
ParentalGenotype: Father: heterozygous for g.951G>A and p.Leu343Pro and Mother: heterozygous for both just like dad
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro)
gnomAD N/A
GT32
Case22: (GT32) Gender, age and ethnicity are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Sister is normal and does not harbor the mutation
ParentalGenotype: Father is heterozygous for the mutation and the mother is normal and does not harbor the mutation
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene:
Variant: NM_000419.3:c.1919_1920del
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940685
gnomAD N/A
54
Case3: (GT54), Gender, age and ethnicity not reported
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: 1 sister that are heterozygous for g.951G>A and p.Leu343Pro
ParentalGenotype: Father: heterozygous for g.951G>A and p.Leu343Pro and Mother: heterozygous for both just like dad
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NC_000017.11:g.44393555C>T (g.951G>A promoter variant) and NM_000419.3:c.1028T>C (p.Leu343Pro)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA913189168 (promoter variant) and CA399804619 (p.Leu343Pro)
gnomAD N/A
GT15
Case34: (GT15) Gender, age and ethnicity have not been specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: Mother and father are heterozygous for this mutation
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NM_000419.3:c.1753-1G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399802017
gnomAD N/A
GT37
Case11:(GT37) Gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NM_000419.3:c.1234G>A (p.Gly412Arg)
LegacyVariant: N/A
ClinVar: 381748
CAiD: CA8603182
gnomAD MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T
GT51
Case27: (GT51) Gender, age and ethnicity are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NM_000419.3:c.3115_3119dup
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940262
gnomAD N/A
68
Case8: (GT68) Gender, age and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Inclusion criteria were patients with a history of mucocutaneous bleeding (Figure 1 shows a bar diagram of all the clinical manifestations in the patient cohort in this article)
CaseNotHPOs: N/A
ProteinExpression: Platelet receptor alphaIIbbeta3 protein was analyzed by flow cytometry followed by western blotting
Platelet Aggregation: Inclusion criteria for probands was absent or reduced platelet aggregation with agonists such as ADP, adrenaline, arachidonic acid, and collagen (no mention of ristocetin here-- this article does not tell us the specific aggregation for each proband in the paper)
CasePreviousTesting: For mutation analysis of ITGA2B and ITGB3 genes, DNA extraction from whole blood, PCR, heteroduplex PCR followed by CSGE and DNA sequencing were performed. All 30 exons of ITGA2B and 15 exons of ITGB3, as well as their promoters, were analyzed by CSGE following heteroduplex PCR.
Gene: ITGA2B
Variant: NM_000419.3:c.641T>C (p.Leu214Pro)
LegacyVariant: N/A
ClinVar: 2901
CAiD: CA115848
gnomAD N/A
From thrombasthenia to next generation thrombocytopenia: Neonatal alloimmune thrombocytopenia induced by maternal Glanzmann thrombasthenia
PMID: 30216638
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions mothers with GT and their newborns. Table 1 shows very general/vague genetic data for the mothers, it is not easy to determine what the actual genetic defects are from Table 1; therefore, there is insufficient evidence
Platelets contribute to amyloid-β aggregation in cerebral vessels through integrin αIIbβ3–induced outside-in signaling and clusterin release
PMID: 27221710
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT probands with variants in ITGA2B or ITGB3
Allogeneic Hematopoietic Stem Cell Transplantation in Glanzmann Thrombasthenia Complicated by Platelet Alloimmunization
PMID: 21567370
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with GT; however, no mention of the proband with variants in ITGA2B and ITGB3
14
Case14: Female, Arab, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0000225, HP:0031364, HP:0000132
(Epistaxis, gingival bleeding, ecchymosis, menorrhagia)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.409-2_419del
LegacyVariant: N/A
ClinVar: 2889
CAiD: CA10575471
gnomAD: N/A
16
Case16: Male, Arab, age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Table 1 mentions family history available for the proband, however no specific details about family provided in paper
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.409-2_419del
LegacyVariant: N/A
ClinVar: 2889
CAiD: CA10575471
gnomAD: N/A
A Two–Amino Acid Insertion in the Cys146–Cys167 Loop of the aIIb Subunit Is Associated with a Variant of Glanzmann Thrombasthenia
PMID: 9739052
Gene: ITGA2B
HGNC: 6138
[Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology]
PMID: 35395997
InsufficientEvidence: Article in Chinese, and variant reported doesn't have a corresponding shift reported in humans.
The Role of Conserved Amino Acid Motifs within theIntegrinb3Cytoplasmic Domain in Triggering FocalAdhesion Kinase Phosphorylation*
PMID: 9065456
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B and/or ITGB3; however, no specific GT probands are mentioned harboring these variants mentioned therefore there is insufficient evidence
Qualitative disorders of platelets and megakaryocytes
PMID: 16102044
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article mentions variants in ITGA2B; however, the variants are not linked to individuals bearing them therefore we have insufficient evidence
Patient‐III6
Case2: Female, Israeli-Arab, (age is either 3 or 8)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: See Fig 1C for pedigree
ParentalGenotype: See Fig 1C for pedigree
CasePresentingHPOs: HP:0000421, HP:0031364, HP:0000967, HP:0002239
(Severe epistaxis, ecchymosis, petechiae, GI bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: No surface expression of αIIbβ3 was found in patients’ platelets (See Fig 3)
PlateletAggregation: N/A
CasePreviousTesting: DNA fragments containing exons and flanking intronic regions of the aIIb and B3 genes were amplified by PCR using primers
Gene: ITGA2B
Variant: NM_000419.3:c.97A>G (p.Asn2Asp)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399806951
gnomAD: N/A
6FL
Case6: Patient FL (found in the GT database) gender and age are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978, HP:0006298 Bruising and prolonged bleeding after tooth extraction
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: 7-10% GPIIIa and GPIIb surface expression
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1063G>A (p.Glu355Lys)
LegacyVariant: (p.Glu324Lys)
ClinVar: 2899
CAiD: CA115844
gnomAD: MAF in the European (non-Finnish) population is 0.00001978 https://gnomad.broadinstitute.org/variant/17-42461008-C-T
PreviouslyPublished: Reference 17 in this article
Frankfurt I
Case3: Patient Frankfurt I (can be found in the GT database)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0006298 Prolonged bleeding after tooth extraction
CaseHPOFreeText: Blood transfusions were needed
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: 24% GPIIIa and GPIIb surface expression
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.620C>T (p.Thr207Ile)
LegacyVariant: (p.Thr176Ile)
ClinVar: N/A
CAiD: CA399805570
gnomAD: N/A
PreviouslyPublished: PMID: 1602006
Chinese 10
Case13: Patient Chinese10 (can be found in the GT database) gender and age are not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000979, HP:0000967 (Epistaxis, gingival bleeding, menorrhagia, purpura/petechiae)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: <2% GPIIIa and GPIIb surface expression
PlateletAggregation: N/A
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1750C>T (p.Arg584Ter) authors state they could not find the second variant
LegacyVariant: N/A
ClinVar: 2892
CAiD: CA115834
gnomAD: MAF in the East Asian population is 0.0002176 for the Arg584Ter variant
PreviouslyPublished: Reference number 23 in this article
Hematologically Important Mutations: Glanzmann Thrombasthenia
PMID: 9215749
Gene: ITGA2B and ITGB3
HGNC: 6138 abd 6156
Platelet and granulocyte alloimmunisation in multitransfused Tunisian patients
PMID: 16104882
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: The purpose of our study was to determine the frequency of alloimmunisation against platelets and leukocytes in multiply transfused Tunisian patients; there are 3 GT probands in this article; however, no mention of variants in ITGA2B and/or ITBG3; therefore, we have insufficient evidence
A six-year-old boy
Case1: Male, 6 years old
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0004406, HP:0000967
(Recurring nosebleed, petechia)
CaseHPOFreeText: Diffused peliosis
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: aIIb and b3 were absent in the platelets of this patient analyzed by flow cytometry.
PlateletAggregation: There was no concentration aggregation action in response to ADP and adrenaline, but patient platelets could aggregate when treated by ristocetin
CasePreviousTesting: Genomic DNA was isolated from cells, and exon 4 of ITGA2B was amplified. PCR products were resolved via agarose gels, purified for sequencing.
Gene: ITGA2B
Variant: NM_000419.3:c.480C>G and NM_000419.3:c.574+5G>C
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399805892 and CA913203563
gnomAD: MAF in the East Asian population 0.00005507 http://gnomad.broadinstitute.org/variant/17-42463013-G-C
A naturally occurring mutation near the C terminus of the β‐propeller of αIIb impair the transport of αIIbβ3 complexes from the endoplasmic reticulum to the Golgi apparatus
PMID: 15946231
Gene: ITGA2B
HGNC: 6138
GT11
Case#: 15 year old, female
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, HP:0006298, HP:0001892
PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
Allele 1:
ClinVar: 953046
CAID: CA399802348
Variant: NM_000419.5:c.1651C>T
GnomAD: Highest in East Asian population at a rate of 0.00005045 (1/19820)
Allele 2:
ClinVar: 225393
CAID: CA290947544
Variant: NM_000419.5:c.2333A>C
GnomAD: East Asian: 0.0001087 (2/18394)
ExpressionEvidence:Flow Cytometry of platelet integrin: 7.7% B3 expression, .82% A2B expression
GT20
Case#: 4 year old, male
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, HP:0004406, HP:0006298, HP:0001892
PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
Allele1:
CAID: CA399805892
ClinVar: 953024
Variant:NM_000419.5:c.480C>G
Allele2:
CAID:
ClinVar:
Variant: Not a valid allele. ReferencesDatabase::convertToUnsplicedRegion() - intronic position inside exon ?
ExpressionEvidence: Flow Cytometry of platelet integrin: 53.4% B3 expression, 5.2% A2B expression
GT14
Case#: 39 year old, male
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0000967, HP:0000978, HP:0000225, HP:0004406, HP:0006298, HP:0001892
PlateletAgreggation: Defective response to ADP, Adrenaline, Collagen, Arachidonic acid. Normal response to Ristocetin.
GenotypingMethod: Genomic DNA was extracted from peripheral blood leukocytes for mutational analysis of the αIIb and β3 genes by DNA sequencing
Allele 1:
ClinVar: 2891
CAID: CA115831
Variant: NM_000419.5:c.2621T>G
GnomAD: European at rate of (9494/21600) 0.4395 and East Asian at 0.4327
Allele 2:
ClinVar: 225393
CAID: CA290947544
Variant: NM_000419.5:c.2333A>C
GnomAD: East Asian at a rate of 0.0001087 (2/18394)
ExpressionEvidence: Flow Cytometry of platelet integrin: 83.9% B3 expression, 4.4% A2B expression
Patient 3
Case3: Male, 10 years old, Korean
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: Figure 1 shows haplotype analysis
CasePresentingHPOs: HP:0001342
(Cerebral hemorrhage)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry analyses revealed decreased expression at 7.2%/5.0% of the normal amount of CD41/CD61
PlateletAggregation: Platelet aggregation tests were performed to evaluate responses to ADP, collagen, epinephrine, and ristocetin agonists
CasePreviousTesting: Polymerase chain reaction for all exons ofITGA2Band/orITGB3were performed using primers. Sequence analysis was performed with reference to M_000419.3 andNP_000410.2 forITGA2Band NM_000212.2 and NP_000203.2 for ITGB3.
Gene: ITGA2B
Variant: NM_000419.3:c.2333A>C (p.Gln778Pro) and NM_000419.3:c.975del
LegacyVariant: N/A
ClinVar: 225393
CAiD: CA290947544 and CA915940385
gnomAD: MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-42453691-T-G
Platelet collagen receptor Glycoprotein VI-dimer recognizesfibrinogen and fibrin through their D-domains, contributing toplatelet adhesion and activation during thrombus formation
PMID: 29210180
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: Article does not mention GT probands with specific variants in ITGA2B and/or ITGB3
Novel mutations in Thai patients with glanzmann thrombasthenia
PMID: 28888044
Gene: ITGA2B
HGNC: 6138
F2.II.1
Case#: 17 year old male
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0032438, HP:0001873 PLT anisocytosis, Thrombocytopenia
CaseNotHPOs: HP:0001892
Abnormal Bleeding
FamilyInfo: Pedigree figure 1. Mother, affected, had significant bleeding abnormalities, brother also affected with frequent epistaxis but PLT normal counts
PlateletAgreggation: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA. Ristocetin not assessed in individual per supplementary table
GenotypingMethod: genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.
ClinVar: 50233
CAID: CA10575573
Variant: NM_000419.5:c.3076C>T
GnomAD: Not Found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 45%, CD61 (GPIIIa) 46%, and CD42b (GPIb) 111%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
F5.III.1
Case#: Female, 16
Disease: Glazmann's Thrombasthenia Like Syndrome
CasePresentingHPOs: HP:0000978,HP:0400008
Bruising susceptibility, menometrorrhagia
CaseNotHPOs: NA
FamilyInfo: Pedigree figure 1. Family history of thrombocytopenia.
PlateletAgreggation: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA, with abnormal ristocetin agglutination.
GenotypingMethod: Genetic analysis of ITGA2B and ITGB3 genes was performed by next-generation sequencing (NGS). Sanger sequencing used to confirm variants.
ClinVar: Not Found
CAID: CA399789515
Variant: NM_000419.5:c.3020G>T
GnomAD:Not Found
ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 48%, CD61 (GPIIIa) 50%, and CD42b (GPIb) 104%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).
6.
Case6: "French gypsy mutation in the Manouche tribe" No specific gender or age specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Often severe bleeding (very general-- no other information given on phenotypes)
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: Minimal information, not specific enough
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1544+1 G>A (p.Val513Leufs71*)
LegacyVariant: N/A
ClinVar: 2895
CAiD: CA10575473
gnomAD: N/A
11.
Case11 : Female, age not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: Severe bleeding on occasion
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: N/A
PlateletAggregation: Minimal information, not specific enough
CasePreviousTesting: Sanger sequencing identified disease-causing variants in 18 out of 20 patients (Probands 6 and 14 excluded) with istoantibodies to αIIbβ3. The mutations were evenly distributed between ITGB3 and ITGA2B.
Gene: ITGA2B
Variant: NM_000419.3:c.2095-19T>A and NM_000419.3:c.2770C>T (p.Gln924Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940312 and CA399792054
gnomAD: N/A
Patient 1
Case1: Patient 1, diagnosed at 4 years, gender and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000978, HP:0000421
(Easy bruising, epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Immunoblot analysis of platelet lysates showed no detectable pro-αIIb or mature αIIb in any of the patient samples
PlateletAggregation: Absent in vitro platelet aggregation in response to ADP, epinephrine, and collagen
CasePreviousTesting: Polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and DNA sequencing was performed for ITGA2B
Gene: ITGA2B
Variant: NM_000419.3:c.475G>A (p.Gly159Ser)
LegacyVariant: p.Gly128Ser
ClinVar: N/A
CAiD: CA8603454
gnomAD: MAF in the South Asian population is 0.00003267 http://gnomad.broadinstitute.org/variant/17-42463018-C-T
Three novel β-propeller mutations causing Glanzmann thrombasthenia result in production of normally stable pro-αIIb, but variably impaired progression of pro-αIIbβ3 from endoplasmic reticulum to Golgi
PMID: 16359515
Gene: ITGA2B
HGNC: 6138
Patient 3
Case3: Patient 3, diagnosed at 21 years, gender and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: 2 affected aunts died of bleeding complications before 10 years of age
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000225
(Gingival bleeding)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Immunoblot analysis of platelet lysates showed no detectable pro-αIIb or mature αIIb in any of the patient samples. Trace amounts of Beta3 were detected in samples from this patient
PlateletAggregation: Absent in vitro platelet aggregation in response to ADP, epinephrine, and collagen but a normal initial phase response to ristocetin
CasePreviousTesting: Polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) analysis, and DNA sequencing was performed for ITGA2B
Gene: ITGA2B
Variant: NM_000419.3:c.1162G>A (p.Gly388Ser)
LegacyVariant: p.Gly357Ser
ClinVar: N/A
CAiD: CA8603212
gnomAD: N/A (This variant is not in gnomAD but is in ExAC)
A 10-Base-Pair Deletion in the Gene Encoding Platelet GlycoproteinIIb Associated with Glanzmann Thrombasthenia in a Horse
PMID: 17338169
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article discusses a 10 base pair deletion in GT; however, in a horse, not human therefore there is insufficient evidence
Molecular Basis for Glanzmann’s Thrombasthenia (GT) in a Compound Heterozygote With Glycoprotein IIb Gene: A Proposal for the Classification of GT Based on the Biosynthetic Pathway of Glycoprotein IIb-IIIa Complex
PMID: 1317725
Gene: ITGA2B
HGNC: 6138
Glanzmann thrombasthenia detected because of knee hemarthrosis: a case report
PMID: 20736850
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with GT; however, no variants in ITGA2B or ITGB3 are mentioned
A Point Mutation in the Integrin p3 Cytoplasmic Domain (S752 + P) Impairs Bidirectional Signaling Through aIIbP3 (Platelet Glycoprotein IIb-IIIa)
PMID: 8080992
Gene: ITGB3
HGNC: 6138
InsufficentEvidence: This article mentions a variant in ITGB3; however, the article does not mention a GT case report with the variant in detail, rather this paper cites another paper of a proband harboring the variant of interest
Glanzmann'sThrombastheniaProposedOptimalManagementDuringSurgeryandDelivery
PMID: 12812388
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a 34 year old proband with GT; however, there is no mention of variants in ITGA2B and/or ITGB3 in the proband that is mentioned
Successful surgery using recombinant factor VIIa for recurrent, idiopathic nonulcer duodenal bleeding in a patient with Glanzmann's thrombasthenia
PMID: 12353868
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
Spontaneous hemarthrosis in combined Glanzmann thrombasthenia and type 2N von Willebrand disease.
PMID: 24418945
Gene: ITGA2B
HGNC: 6138
Glanzmann's thrombasthenia in North Indians: Sub classification and carrier detection by flow cytometry
PMID: 19172516
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions individuals with GT; however, there are no variants in ITGA2B and/or ITGB3 mentioned here
Insertion of a C in the exon 28 of integrin αIIb gene leading to a frameshift mutation is responsible for Glanzmann thrombasthenia in a Japanese case
PMID: 15748238
Gene: ITGA2B
HGNC: 6138
Endometriosis in two sisters with Glanzmann's thrombasthenia
PMID: 19647234
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions two individuals with GT; however, there is no mention of variants in ITGA2B and/or ITGB3
Platelet Glycoprotein IIb-III, (ffIIbp3 Integrin) Confers Fibrinogen- and Ac tiva tion-Dependen t Aggregation on Heterologous Cells
PMID: 2070074
Gene: N/A
HGNC: N/A
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence
Note: Although there is no evidence regarding GT probands and variants-- there is some experimental assay evidence, where methods for the experiment may be useful
Glanzmann's thrombasthenia and pregnancy: report of a case and literature review
PMID: 22384307
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with GT however there are no variants in ITGA2B or ITGB3 mentioned
Inherited platelet disorders
PMID: 22726100
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This review mentions variants in ITGA2B and ITGB3; however, variants are not tied to specific probands therefore there is insufficient evidence
Inherited platelet disorders and oral health
PMID: 22583386
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention probands or variants with GT however this has a general summary of Glanzmann thrombasthenia
Patient C
Case: (Patient C), Male, age, and ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: 2 siblings (compound heterozygotes for the p.Cys674Arg and p.Ile374Thr mutation)
ParentalGenotype: Mother: (p.Ile374Thr) and Father: (p.Cys674Arg)
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: By immunoblot analysis, it was found that the platelets of the patient and his 2 siblings contained both αIIb and β3, but at reduced levels compared with a healthy control (Figure 1B)
CasePreviousTesting: Direct sequence analysis of the of the genes encoding αIIb were performed on DNA isolated from leukocytes obtained from Patient C and family members.
Gene: ITGA2B
Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.2113T>C (p.Cys705Arg)
LegacyVariant: (p.Ile374Thr) and (p.Cys674Arg)
ClinVar: N/A
CAiD: CA290950815 and CA8602816
gnomAD: MAF in the European (non-Finnish) population is 0.000008792 https://gnomad.broadinstitute.org/variant/17-42455140-A-G
Patient M
Case: (Patient M) Gender, age, ethnicity are not specified
DiseaseAssertion: Glanzmann thrombasthenia (diagnosed at 1 year old)
FamilyInfo: N/A
ParentalGenotype: Mother: (p.Val298Phe) and Father: (p.Tyr380Ter)
CasePresentingHPOs: (Went to Reference #17 to see what lab findings/phenotypes were reported for this patient; however, access not available to this article)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
ProteinExpression: By immunoblot analysis, both αIIb and β3 subunits were detected in the patient's platelet lysates, but at reduced levels compared to a healthy control and samples from both parents (Figure1A)
CasePreviousTesting: Direct sequence analysis of the of the genes encoding αIIb were performed on DNA isolated from leukocytes obtained from Patient M and family members
Gene: ITGA2B
Variant: NM_000419.3:c.985G>T (p.Val329Phe) and NM_000419.3:c.1232dup (Tyr411Ter)
LegacyVariant: (p.Val298Phe) and (p.Tyr380Ter)
ClinVar: N/A
CAiD: CA399804719 and CA915940593
gnomAD: MAF in the South Asian population is 0.0001312 https://gnomad.broadinstitute.org/variant/17-42458407-G-A
Glanzmann thrombasthenia: An update
PMID: 19854165
Genes: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article describes many variants in ITGA2B and ITGB3 however no probands to tie variants to therefore insufficient evidence
Hematological and surgical management in Glanzmann's thrombasthenia: A case report
PMID: 24739923
Gene: ITGA2B and/or ITGB3 (These genes may be involved since this patient has GT)
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case report of an individual with Glanzmann thrombasthenia; however, there are no ITGA2B or ITGB3 variants in this proband
Case8: Patient GM, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1
PlateletAggregation: See Table 1
CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
Gene: ITGA2B
Variant: NM_000419.3:c.1139G>A (p.Gly380Asp) and NM_000419.3:c.2254C>T (p.Leu721Val) and NM_000419.3:c.2264G>C
LegacyVariant: (p.Gly349Asp)
ClinVar: N/A
CAiD: CA8603217 and CA500266743 and CA8602772
gnomAD: MAF in the European non Finnish population is 0.00001060 https://gnomad.broadinstitute.org/variant/17-42454380-C-G
Case16: Patient PV, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1
PlateletAggregation: See Table 1
CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
Gene: ITGA2B
Variant: NM_000419.3:c.2254C>T (p.Leu721Val) and NM_000419.3:c.2264G>C
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA500266743 and CA8602772
gnomAD: MAF in European non F is 0.00001060
Case17: Patient VA, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1
PlateletAggregation: See Table 1
CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
Gene: ITGA2B
Variant: NM_000419.3:c.2555del
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940767
gnomAD: N/A
Case12: Patient ER, gender and age are not specified, all of these patients are Caucasian (either Italian or European)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: All patients presented with a current or past history of bleeding and a bleeding time >15 min. Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who bled only after trauma or surgery or had minor symptoms, such as epistaxis. Moderate/severe bleeders were defined as those with a history of spontaneous or life threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusions
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Table 1
PlateletAggregation: See Table 1
CasePreviousTesting: To identify point mutations responsible for GT, we have sequenced all coding regions of Ib and 3 genes and intron/exon boundaries.
Gene: ITGA2B
Variant: NM_000419.3:c.1912dup
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940678
gnomAD: N/A
Norethisterone therapy for bleeding due to gastrointestinaltelangiectases in Glanzmann’s thrombasthenia
PMID: 9504647
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
Pyelolithotomy in a patient with Glanzmann thrombasthenia andantiglycoprotein IIb/IIIa antibodies: the shortest possibleduration of treatment with recombinant activated factor VII andplatelet transfusions
PMID: 12718376
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: Thus article mentions a Glanzmann thrombasthenia proband; however, no variants in ITGA2B and/or ITGB3 were reported in this patient
Role of RFLP using TspRI for carrier detection in Glanzmann’s thrombasthenia: a report on two families M. KANNAN Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author B. K. YADAV Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author F. AHMAD Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author R. SAXENA Department of Hematology, All India Institute of Medical Sciences, New Delhi, IndiaSearch for more papers by this author
PMID: 19170775
Gene: ITGA2B
HGNC: 6138
Two male patients
Case2: Male, age not specified, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: See Fig 3
ParentalGenotype: Both mutations were found to be heterozygous in all family members that includes parents
CasePresentingHPOs:
(Gum bleeding, ecchymosis, epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed that the surface expression of GPIIb/IIIa in patients was 0% and both parents also showed reduced expression as well.
PlateletAggregation: Platelet aggregation in response to all the agonists except risocetin was completely absent in the patient
CasePreviousTesting: Mutation screening by conformational sensitive gel electrophoresis was performed in all the 30 exons of ITGA2B and 15 exons of ITGB3 gene in this patient
Gene: ITGA2B
Variant: NM_000419.3:c.1028T>C (p.Leu343Pro) and a promoter variant g.951G>A
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399804619
gnomAD: N/A
59/M
Case#: Patient ID 5, Male 59 years old. North Indian
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0031364, HP:0003540,
Ecchymosis, Impaired platelet aggregation
PlateletAgreggation: LTA with ADP, Epi, Coll, AA, and Ristocetin: Impaired with all agonists
GenotypingMethod: Next generation sequencing. Sanger sequencing used to confirm pathogenic variants
ClinVar: NA
CAID: CA8603099
Variant: NM_000419.5:c.1424_1427dup
GnomAD: South Asian at a rate of (.0001960) 6/306160
ExpressionEvidence: NA
58/F
Case#: Patient ID 3, Female 58 years old. North Indian
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0031364, HP:0003540, HP:0000421, HP:0000132, HP:0000967
Ecchymosis, Impaired platelet aggregation, Epistaxis, Menorrhagia, Petechiae
PlateletAgreggation: LTA with ADP, Epi, Coll, AA, and Ristocetin: Impaired with all except Ristocetin
GenotypingMethod: Next generation sequencing. Sanger sequencing used to confirm pathogenic variants
ClinVar: 953042
CAID: CA399804619
Variant: NM_000419.5:c.1028T>C
GnomAD: Not Found
ExpressionEvidence: Flow Cytometry for platelet expression of GPIIb/IIIa in CD41a 0% and CD61 14.8%.
DDAVP-induced enhancement of platelet retention: Its dependence on platelet-von Willebrand Factor and the platelet receptor GP IIb/IIIa
PMID: 1499698
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient (29 years old); however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence. The aim of the present study was to investigate the mechanism by which DDAVP induces increased platelet adhesiveness, as measured in a platelet retention test.
Plat el et Vitro nec t in Receptor Exp res s ion Differentiates Iraqi - Jewi s h From Arab Patients With Glanzmann Thrombasthenia in Israel
PMID: 1949709
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article examined platelets of the Iraqi-Jewish and Arab Glanzmann thrombasthenia population; however, no specific proband information or variants in ITGA2B and/or ITGB3 were mentioned. This could be classified as "NoEvidence"; however, due to the fact the article mentioned two specific populations, I have noted it under "InsufficientEvidence"
Deep Vein Thrombosis, Raynaud's Phenomenon, and Prinzmetal Angina in a Patient with Glanzmann Thrombasthenia
PMID: 23346430
Gene: ITGA2B
HGNC: 6138
Case1: Female, 6 years old, Chinese
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Pedigree available (See Figure 1)
ParentalGenotype: Parents are non-symptomatic
CasePresentingHPOs: HP:0000421 (Epistaxis)
CaseHPOFreeText: Mucocutaneous hemorrhages
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed that GPIIb and GPIIIa were significantly reduced in the patient indicating type 1 GT. (See Figure 2 for data)
PlateletAggregation: Platelet aggregation in response to ADP, collagen, adrenaline, thrombin and arachidonic acid was markedly decreased compared to that of controls, while ristomycin induced platelet aggregation was normal
CasePreviousTesting: DNA was extracted, all coding regions of the ITGA2B and ITGB3 genes were amplified by PCR using primers. PCR products were electrophoresed on agarose gel and then purified. Purified DNA samples were labeled and then analyzed using an automated sequencer
Gene: ITGA2B
Variant: NM_000419.3:c.2930del and c.1544-1delG (not registered)
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA915940386
gnomAD: N/A
paternal uncle
Case3: Male, age not specified, Cypriot (paternal uncle of 3 year old)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Brother and brother's daughter were also affected with same mutation (See Figure 3 for family pedigree)
ParentalGenotype: Parents were heterozygous for same mutation (See Figure 3 pedigree)
CasePresentingHPOs: HP:0000225, HP:0000421, HP:0031364
(Gingival bleeding, epistaxis, ecchymosis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets
PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation
CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.
Gene: ITGA2B
Variant: M_000419.3:c.605T>G (p.Phe202Cys)
LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)
ClinVar: N/A
CAiD: CA399805605
gnomAD: N/A
her father
Case2: Male, age not specified, Cypriot (father of 3 year old)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: Daughter and brother were also affected with same mutation (See Figure 3 for family pedigree)
ParentalGenotype: Parents were heterozygous for same mutation (See Figure 3 pedigree)
CasePresentingHPOs: HP:0000225, HP:0000421, HP:0031364
(Gingival bleeding, epistaxis, ecchymosis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed decreased surface expression of αIIb and β3 in patients' platelets
PlateletAggregation: Absent platelet aggregation in response to ADP, epineprhine, collagen but normal ristocetin induced platelet aggregation
CasePreviousTesting: SSCP analysis of the αIIb gene in the three patients revealed an altered pattern of migration of the DNA fragment containing exons 5 and 6 and their flanking intronic regions.
Gene: ITGA2B
Variant: M_000419.3:c.605T>G (p.Phe202Cys)
LegacyVariant: (p.Phe171Cys) + 31= (p.Phe202Cys)
ClinVar: N/A
CAiD: CA399805605
gnomAD: N/A
Presentation and Pattern of Symptoms in 382 PatientsWith Glanzmann Thrombasthenia in Iran
PMID: 15389911
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article looks at the presentation and pattern of symptoms in 382 patients with GT. There are no variants associated with probands in ITGA2B and/or ITBG3
Use of rFVIIa in 4 children with Glanzmann thrombasthenia.
PMID: 17023825
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions individuals with GT; however, there is no mention of these individuals bearing variants in ITGA2B and/or ITBG3
Acute Epidural Hematoma in a PatientWith Glanzmann's Thrombasthenia—Case Report—
PMID: 21030808
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a 7 year old girl with GT; however, there are no variants in ITGA2B or ITGB3 mentioned in this article
GT10
Case10: GT-10, Caucasian, gender or age not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: Mother: 3091delC heterozygous and Father: c.1210_105A>G heterozygous
CasePresentingHPOs: N/A
CaseHPOFreeText: Bleeding symptoms are severe and bleeding time is pathogenic (See Table 1) Abstract mentions patients' bleeding signs include epistaxis, mucocutaneous bleeding, haematomas, petechiae, GI bleeding and menorrhagia; however, not specified per proband.
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry was performed and expression is stated as pathogenic in Table 1
PlateletAggregation: Platelet aggregation was performed and is stated as pathogenic in Table 1; however, no specific agonists mentioned
CasePreviousTesting: All exons of ITGA2B and ITGB3 genes as well as surrounding intron regions were amplified by PCR using intronic primers as pre-viously described (12). The purified DNA fragments were then di-rectly sequenced.
Gene: ITGA2B
Variant: NM_000419.3:c.1210+105A>G and NM_000419.3:c.3091del
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA290953790 and CA915940322
gnomAD: N/A
Patient ID 9
Case#: Patient ID 9, Female, Korean
Disease: Glazmann's Thrombasthenia
CasePresentingHPOs: HP:0001892, HP:0000978
Abnormal Bleeding, Bruising susceptibility
PlateletAgreggation: Decreased response to ADP, COL, EPI, normal response to RIS
GenotypingMethod: Targeted Exome sequencing followed by Whole exome sequencing performed.
Allele 1:
ClinVar:Not Found
CAID: CA2573131754
Variant: NM_000419.5:c.2390del
GnomAD: Not Found
Allele 2
ClinVar: 225393
CAID:CA290947544
Variant: NM_000419.5:c.2333A>C
GnomAD:East Asian at rate of 0.0001087 (2/18394)
ExpressionEvidence: Decreased CD41 expression by flow cytometry
GT7
Case: 20 year old female French Gypsy
CasePresentingHPOs: HP:0001975
(Decreased platelet glycoprotein IIb-IIIa)
GenotypingMethod:Genotyping analysis of the HPA-1 system by high resolution melting analysis (methods not provided, cited article I don't have access too)
not highly specific mutation: "p.Gln228/p.Arg584"
Allele1
ClinVar: Not found
CAID: PA913203366
Variant: NP_000410.2:p.Gln228Ter
GnomAD: not found
Allele 2
ClinVar: Not found
CAID: PA115836
Variant: NP_000410.2:p.Arg584Ter
GnomAD: Not found
ExpressionEvidence: "Severe defective surface expression" of platelet surface αIIbβ3 integrin (methods not provided cited article no access too)
Acquired thrombasthenia due to GPIIbIIIaplatelet autoantibodies in a 4-yr-old child
PMID: 15748238
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions proband with acquired thrombasthenia; however, there is no mention of variants in ITGA2B and/or ITGB3
proband
Case#: Peretz_1995_proband. 26 y.o. female. Iranian-Jewish
DiseaseAssertion: Glanzmann's Thrombasthenia
FamilyInfo: consanguineous, 1 of 2 brothers were affected (affected was homozygous for variant, unaffected was homozygous for normal, both siblings with no platelet aggregation with ADP, collagen, epinephrine, and normal response to ristocetin. Their clot retraction was absent and the binding of monoclonal antibody (MoAb) 10E5, which recognizes the GPIIb/IIIa complex,26 was minimal.
ParentalGenotype: heterozygous, both
CasePresentingHPOs:
PlateletAggregation: no platelet aggregation in response to adenosine diphosphate, collagen, or epinephrine and had a normal response to ristocetin.
CaseHPOFreeText: moderate mucocutaneous bleeding
CaseNotHPOs:
CaseNotHPOFreeText:
ProteinExpression: heterodimer in transfected COS-7 cells resulted in low peroxidase activity, indicating lack of surface expression of the heterodimer.
CasePreviousTesting:
Method: Testing was through southern blot analysis with restriction enzymes and amplification of fragments
PreviouslyPublished:
Gene: ITGA2B
Variant: 6-bp deletion and 31-bp insertion in exon 25 of the GPIIb gene - altered C-terminal sequence of 105 amino acids starting at Val-825 - substitution of 10 amino acids Leu817-Asn826 by an altered sequence of 8 amino acids
HGVS: NM_000419.5:c.2473_2478delinsTCACCAGGGCCTTCACGTGAGCATGGAGAG
ClinVar:
CAID: CA2581931358
gnomAD: No matching variants found
PeriodontalManagementofGlanzmann'sThrombasthenia:Reportof3Cases
PMID: 8866321
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions 3 Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in these individuals; therefore, we have insufficient evidence
A Glanzmann’s mutation in β3 integrin specifically impairs osteoclast function
PMID: 11342577
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions variants in ITGA2B/ITGB3; however, there is no mention of individual(s) with GT therefore we have insufficient evidence
Characterization of the cDNA and genomic DNA sequence encoding for the platelet integrin alpha IIB and beta III in a horse with Glanzmann thrombasthenia
PMID: 22210999
Gene: ITGA2B
HGNC: 6138
InsufficientEvidence: This article mentions a variant in ITGA2B; however, it is examined in a horse not human
Molecular analysis of a patient with type I Glanzmannthrombasthenia and clinical impact of the presenceof anti-aIIbb3 alloantibodies
PMID: 21136216
Gene: ITGB3
HGNC: 6138
The Level of Laboratory Testing Requiredfor Diagnosis or Exclusion of a PlateletFunction Disorder Using Platelet Aggregationand Secretion Assays
PMID: 19408197
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article provides background information on Glanzmann thrombasthenia; however, does not mention probands or variants in ITGA2B and ITGB3
Thrombin generation assays: accruing clinical relevance.
PMID: 15257016
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention GT patients with variants in ITGA2B and/or ITGB3; however, this may be useful for experimental assay purposes
DentalConsiderationsforaGlanzmann'sThrombastheniaPatient:CaseReport
PMID: 8724714
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
Platelet Fibrinogen and Vitronectin in Glanzmann Thrombasthenia: Evidence Consistent With Specific Roles for Glycoprotein IIb/IIIa and a,P3 Integrins in Platelet Protein Trafficking
PMID: 1726706
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia patients/probands with variants in ITGA2B and/or ITGB3; therefore, there is no evidence to report
ITGA2B and ITGB3 gene mutations associated withGlanzmann thrombasthenia
PMID: 29125375
Gene: ITGA2B and ITBG3
HGNC: 6138 and 6156
NoEvidence This article gives a general overview of Glanzmann thrombasthenia, it does not discuss a proband or variants within probands.
Congenital disorders associated with platelet dysfunctions.
PMID: 18278172
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions Glanzamnnt thrombasthenia variants; however, these variants are not tied to individual probands
Hematuria: An uncommon presentation of Glanzmann's thrombasthenia—Lessons learnt
PMID: 20535297
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a case study of a 55 year old male with GT; however, no variants in ITGA2B/ITGB3 are presented here
GT-13
Case13: GT-13, gender, age, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia type I
FamilyInfo: N/A
ParentalGenotype: Segregation analysis confirmed the presence of heterozygous mutations in carrier parents
CasePresentingHPOs: N/A
CaseHPOFreeText: Article mentions patients presented with variable bleeding diathesis and Table 1 shows the several phenotypes that were seen among the cohort of 13 patients in this study (this article does not state a specific bleeding phenotype for each proband) "Most of the patients had gross blood loss due to epistaxis (54%), cutaneous bleeding (58%) and menorrhagia (100% of women), while other common symptoms (oral cavity, gastrointestinal, following dental extraction or mild injuries, postpartum, or hematomas) were in general milder."
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: Flow cytometry showed <5% of αIIbβ3 expression
PlateletAggregation: Article mentions the disorder was indentified by platelet testing consisting in severely impaired aggregation in response to all physiological agonists and also TMA (See Table 4). Ristocetin-induced platelet aggregation was normal or reduced to some extent.
CasePreviousTesting: To detect mutations in ITGA2B or ITGB3, total RNA from peripheral blood was used for cDNA synthesis for RT-PCR. Using specific oligonucleotides and conditions, they amplified and sequenced ITGA2B and ITGB3 by Sanger sequencing, and every mutation found in cDNA was confirmed on DNA samples
Gene: ITGA2B
Variant: (p.Trp51Ter)
LegacyVariant: N/A
ClinVar: N/A
CAiD: Unregistered Variant
gnomAD: N/A
Platelet-derived Microparticle Formation Involves Glycoprotein IIb-IIIa
PMID: 8325838
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
NoEvidence: This article does not mention Glanzmann thrombasthenia probands with variants in ITGA2B and ITGB3
R to Q amino acid substitution in the GFFKR sequence of the cytoplasmic domain of the integrin IIb subunit in a patient with a Glanzmann's thrombasthenia-like syndrome.
Case1: (Patient A.P) Male, 21 years old, Italian)
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: Biocurator should see Table 1, if any important info to be obtained from here
CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000967, HP:0002249
(Epistaxis, gingival bleeding, petechiae, melena)
CaseHPOFreeText: Hematoma
CaseNotHPOs: N/A
ProteinExpression: As detailed earlier, the main features of A.P.’s platelets are a total αIIbβ3 content that is about half that observed with normal platelets yet with a surface expression that is sparse compared with the size of the internal pool --> observed decrease of αIIbβ3 on the surface of his platelets (approximately 15% of normal levels)
Platelet Aggregation: Aggregation remained defective when ADP was added to PRP anti-coagulated with heparin, and when measured in citrated whole blood by impedance aggregometry in response to ADP, collagen, and arachidonic acid. When ADP was added to washed platelets together with fibrinogen, the aggregation response was somewhat improved. An improved aggregation response was also seen when washed platelets were incubated with collagen (not shown). However, with a-thrombin, a slow and irreversible aggregationwas again observed.
CasePreviousTesting: PCR SSCP of ITGA2B and ITGB3 "To define the genetic defect responsible for the disease, we performed an extensive analysis of the exons of the αIIb and β3 genes using nonradioactive PCR-SSCP methodology developed in our laboratory."
Gene: ITGA2B
Variant: NM_000419.3:c.3077G>A (p.Arg1026Gln)
LegacyVariant: (p.Arg995Gln)
ClinVar: 50232
CAiD: CA10575572
gnomAD MAF in the European (non-Finnish) population is 0.000008801https://gnomad.broadinstitute.org/variant/17-42449775-C-T
PreviouslyPublished: PMID: 1638023
First description of an IgM monoclonal antibody causingaIIbb3integrin activation and acquired Glanzmannthrombasthenia associated with macrothrombocytopenia
PMID: 30868743
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156, respectively as shown above
InsufficientEvidence: Article discusses case report; however, no variants were reported in either ITGA2B or ITGB3 among sequencing analysis for proband.
Patient GT-2
Case2: Female, 20 years old, ethnicity not specified
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: N/A
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: See Figure 4
PlateletAggregation: See Table 2
CasePreviousTesting: N/A
Gene: ITGA2B
Variant: NM_000419.3:c.1366_1371del (p.Val456_Asp457del)
LegacyVariant: (p.Val425_Asp426del)
ClinVar: 2898
CAiD: CA8603160
gnomAD: https://gnomad.broadinstitute.org/variant/17-42458268-TGTCTAC-T
PreviouslyPublished: PMID: 8704171
The Molecular Genetic Basis of Glanzmann’s Thrombasthenia in a Gypsy Population in France: Identification of a New Mutation on the &IIb Gene
PMID: 7620188
Gene: ITGA2B
HGNC: 6138
Note: Article mentions, under materials and methods, that the group being studied are two different families (I and II) belonging to the French gypsy community; however, in the results section the article focuses on patient V.17 from Family 1- therefore patient V.17 is annotated as the proband in this article
Acquired Glanzmann thrombasthenia: From antibodies to anti-platelet drugs
PMID: 31010659
Gene: ITGA2B and ITGB3
HGNC: 6138 and 6156, respectively as shown above
InsufficientEvidence: This is a review article. There are no specific case reports; however, there are cited articles which may have GT probands states in them
PreviouslyPublished: PMIDs: 3015287, 2935559, 8982055, 12437677
A novel form of integrin dysfunction involving β1, β2, and β3 integrins
PMID: 12511588
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with LAD-1 and GT like symptoms however no variants in ITGA2B and/or ITGB3 are mentioned
The role of platelets in venous thrombosis: a patient with Glanzmann's thrombasthenia and a factor V Leiden mutation suffering from deep venous thrombosis
PMID: 12871523
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This mentions a Glanzmann thrombasthenia patient; however, no variants in ITGA2B and/or ITGB3 are mentioned in this patient; therefore, we have insufficient evidence
The proband was a 1-year-old Japanese girl
Case1: Female, 1 year old, Japanese
DiseaseAssertion: Glanzmann thrombasthenia
FamilyInfo: N/A
ParentalGenotype: N/A
CasePresentingHPOs: HP:0000979, HP:0000421
(Purpura, epistaxis)
CaseHPOFreeText: N/A
CaseNotHPOs: N/A
CaseNotHPOsFreeText: N/A
ProteinExpression: The absence of platelet GPIIb-IIIa complexes was con-firmed by flow cytometric and immunoblotting analyses. Figure 1 shows the flow cytometric analysis of the platelets
PlateletAggregation: Absence of platelet aggregation in response to ADP, epinephrine, and collagen but the presence of a normal response to ristocetin
CasePreviousTesting: Genomic DNA was extracted by a standard protocol from the peripheral blood mononuclear cells of the patient and her parents. The flanking region of exon 25 of the GPIIb gene including the introns was amplified by PCR from the genomic DNA.
Gene: ITGA2B
Variant: NM_000419.3:c.2449-1G>C
LegacyVariant: N/A
ClinVar: N/A
CAiD: CA399795582
gnomAD: N/A
Colonoscopy polypectomy management in Glanzmann’s thrombasthenia
PMID: 21160656
Gene: ITGA2B and/or ITGB3
HGNC: 6138 and 6156
InsufficientEvidence: This article mentions a proband with GT; however, no variants in ITGA2B and/or ITGB3 mentioned