PMID: 30097224

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mentions Glanzmann thrombasthenia probands or vairants

PMID: 26096001

Gene: ITGB3 and ITGA2B

HGNC: 6156 and 6138, respectively as shown above

Case20: Patient LPR, 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: ITGB3

Variant: NM_000212.2:c.355C>T and NM_000212.2:c.355C>T

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622924 and CA8623361

gnomAD: MAF in the South Asian population is 0.0001307 https://gnomad.broadinstitute.org/variant/17-45360909-C-T and MAF in the European non Finnish pop is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C

Case24: Patient CI, 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_000212.2:c.1801T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623361

gnomAD: MAF in the European non Finnish population is 0.00001758 https://gnomad.broadinstitute.org/variant/17-45376784-T-C

PMID: 23146053

Genes: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions many variants in ITGA2B and ITGB3; however, no probands are mentioned in this review.

PMID: 1321709

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article is a review on Glanzmann thrombasthenia, it does not mention specific patients or variants in ITGA2B and/or ITGB3; however, it does mention probands in other papers

PreviouslyPublished: PMID: 1702098, 1967954

Case#: Female, 37 (age when studied)

Disease: Glazmann's Thrombasthenia Like Syndrome

CasePresentingHPOs: HP:0001873, HP:0000978, HP:0000225

Thrombocytopenia, bruising susceptibility, gingival bleeding

CaseNotHPOs: NA

FamilyInfo: Pedigree figure 1. Several affected family members, history of thrombocytopenia.

PlateletAgreggation:Sister studied: Decreased PLT aggregation and diminished ATP release with the agonists ADP, collagen, and AA, with normal 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: CA400034393

Variant: NM_000212.3:c.2278C>T (ITGB3)

GnomAD: Not Found

ExpressionEvidence: Level of expression on PLT surface determined by FCM: CD41a (GPIIb/IIIa) 73%, CD61 (GPIIIa) 74%, and CD42b (GPIb) 111%. Healthy control value range: CD41a (GPIIb/IIIa) (85-115%); CD61 (GPIIIa) (80-120%); CD42b (GPIb) (70-130%).

PreviouslyPublished: PMID: 8471765

This proband has been previously published in the PMID listed above --> see that paper to get patient information. This patient can also be found in the GT database

PMID: 25539746

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

Case41: (GT-51) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT49-GT52 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available (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: ITGB3

Variant: NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623443

gnomAD: MAF in East Asian population: 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Case11: (GT-13) Male, carrier, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT11 -GT14 are related to GT-13 see Table 1

ParentalGenotype: Parents may be included in Table 1; however, not specified so no information

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Not available (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: ITGB3

Variant: NM_000212.2:c.727G>C (p.Asp243His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

PMID: 8400280

Gene: ITGB3

HGNC: 6156

PMID: 9246538

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article is a review and goes over many patients from the Glanzmann thrombasthenia database https://glanzmann.mcw.edu/

PreviouslyPublished: All these probands have been previously published in the GT database https://glanzmann.mcw.edu/ please search the database to get info. There are no "new' case reports in this article

Case29: GT40, Female, India, age of onset is 6 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: ITGB3

Variant: NM_000212.2:c.428T>G (p.Leu143Trp)

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252

gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45361875-T-G)

Case18: GT09, Female, India, age of onset is 21 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: ITGB3

Variant: NM_000212.2:c.428T>G (p.Leu143Trp) and NM_000212.2:c.1261G>A (p.Val422Met)

LegacyVariant: N/A

ClinVar: 13567

CAiD: CA123252 and CA400028437

gnomAD: MAF in the Other population is 0.0001629 https://gnomad.broadinstitute.org/variant/17-45361875-T-G

PMID: 24498605

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

Case5: No assertion made on age, gender or ethnicity

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: The identified variants were heterozygote in parents.

CasePresentingHPOs: N/A

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: ITGB3

Variant: NM_000212.2:c.538G>A (p.Gly180Arg) and NM_000212.2:c.155G>T (p.Cys52Phe)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622972 (p.Gly180Arg) CA8622859 (p.Cys52Phe)

gnomAD: "Other" population (p.Gly180Arg) MAF is 0.0001630 https://gnomad.broadinstitute.org/variant/17-45361985-G-A and South Asian population p.Cys52Phe) MAF is 0.00003266.

PMID: 1716379

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

PMID: 20182353

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions an individual with GT; however, there is no mention of ITGA2B and/or ITGB3 variants in this individual

PMID: 12871507

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions probands with GT; however, there are no variants in ITGA2B and/or ITGB3, in these probands noted in the article

Case6: (GT6), Male, 82 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

ProteinExpression: 40-55% 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: ITGB3

Variant: NM_000212.2:c.665T>C (p.Leu222Pro) and NM_000212.2:c.1871G>A (p.Cys592Tyr)

LegacyVariant: (p.Leu196Pro) and (p.Cys624Tyr) (The paper gives legacy and current nomenclature)

ClinVar: N/A

CAiD: CA291224887 and CA400032726

gnomAD MAF in the European (non-Finnish) population is 0.00006482 https://gnomad.broadinstitute.org/variant/17-45363676-T-C

PMID: 33600779

PMID: 10097812

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention GT patients with variants in ITGA2B and/or ITGB3; therefore there is no evidence

Case21: (ProbandGT-21) Male, 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% GPIIIa and GPIIIb surface expression

Platelet Aggregation: N/A

CasePreviousTesting: Promoter and exon sequences of aIIb and b3 genes were amplified and directly sequence

Gene: ITGB3

Variant: NM_000212.2:c.191G>A (p.Cys64Tyr) the second mutation was not identified

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA291224490

gnomAD N/A

PMID: 9226191

Gene: ITGB3

HGNC: 6156

PMID: 16907879

Gene: ITGB3

HGNC: 6156

Case#: II2 Figure 1A, Male, 7yo

DiseaseAssertion: Glanzmann's thrombasthenia

**FamilyInfo: ** Figure 1A, non-consanguineous, sibling (II1) died at 5yo, sibling (II3) in good health, mother and father heterozygous carriers

ParentalGenotype: both parents heterozygous carriers

CasePresentingHPOs: (HP:0001933) subcutaneous bleeding, (HP:0004406) spontaneous epistaxis, (HP:0011858) coagulation factor IX decreased

PlateletAggregation: Platelets were normal, coagulation factors normal, vWF factor normal, bone marrow normal. Platelet count via LH780 automatic blood analyzer, vWF via immunoturbidimetry, CD41(GPⅡb)/CD6l (GPⅢa) and CD42b via flow cytometry.

CaseHPOFreeText:Hemophilia B. Mutation in the F9 gene c.8G > A of unknown clinical significance, considered non-pathogenic.

CaseNotHPOs:

**CaseNotHPOFreeText: **

ProteinExpression: Flow cytometry results revealed that CD41 (GPⅡb) and CD6l (GPⅢa) were 2.05% and 0%, respectively (normal values ​​ranged from 95% to 97%), suggesting that the expression of platelet surface membrane glycoprotein GPIIb/IIIa was significantly reduced.

CasePreviousTesting: Whole exome sequencing verified by Sanger sequencing. Whole gene synthesis, qPRC analysis, Western blotting.

**PreviouslyPublished: **

Gene: ITGB3

Variant: c.1431C > T/p.Gly477 = in ITGB3 exon10 in the proband

HGVS: NM_000212.3:c.1431C>T

**ClinVar: ** 3242396

**CAID: ** CA500651220

gnomAD: Absent

PMID: 12707732

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a Glanzmann thrombasthenia patient with osteoporosis; however, the article does not mention specific variants in ITGA2B and/or ITGB3 in the proband. Rather, the discussion mentions other variants in ITGA2B and/or ITGB3 therefore we have insufficient evidence

PMID: 19657319

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a patient with GT; however, no variants in ITGA2B and/or ITGB3 mentioned here

PMID: 23995838

Gene: ITGB3

HGNC: 6156

PMID: 15134555

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

NoEvidence: This article does not mention Glanzmann thrombasthenia patients or variants in ITAG2B and/or ITGB3. This article gives more background on the molecular mechanisms of Glanzmann thrombasthenia

PMID: 27469266

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

See Page Notes for Supplementary Data

Case1: Female, 29 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: Parents were heterozygous for mutation (parents are first cousins)

CasePresentingHPOs: HP:0001892, HP:0000421, HP:0000225, HP:0000132

(Severe hemorrhagic diathesis, epistaxis, gingival bleeding, menorrhagia)

CaseHPOFreeText: Patients severe hemorrhagic diathesis manifested as epistaxis

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: Amplification of reversely transcribed platelet GP IIIa mRNA by the polymerase chain reaction and subsequent sequence analysis showed a 86-bp deletion, which corresponds to exon i of the GP IIIa gene.

Gene: ITGB3

Variant: NM_000212.2:c.165+1G>T (No other assertion was made about the 2 other variants in this article, just this variant that is mentioned in this annotation)

LegacyVariant: N/A

ClinVar: 13560

CAiD: CA400031853

gnomAD: N/A

Case1: Female, 22 years old, Portugese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Also studied were the patient’s mother (I.2),her father (1.1), and her sister (II.2). Of these family members, only her sister has reported excessive bleeding although platelet aggregation tests were normal for all of them. Consanguinity was present as her parents were cousins.

ParentalGenotype: Parents heterozygous for mutation

CasePresentingHPOs: HP:0000967

(Petechia)

CaseHPOFreeText: Mucocutaneous bleeding

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: <5% surface expression of aIIbb3

PlateletAggregation: Absent with physiologic agonists but agglutination with ristocetin was normal

CasePreviousTesting: We examined each of the 30 exons of the b3 gene and each of the 15 exons of the aIIb gene for migration changes in PCR-SSCP analysis

Gene: ITGB3

Variant:

LegacyVariant:

ClinVar:

CAiD:

gnomAD: N/A

PMID: 1908636

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