Case22: GT20, Female, India, age of onset is 25 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.2186_2187insT (p.Ile730His), NM_000212.2:c.2191_2192delinsG (p.Leu731Gly), NM_000212.2:c.2201_2206del (p.743Gly_735Iledel)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940729, CA915940730, CA915940731

gnomAD: N/A

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

Case25: GT32, Male, 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

Case28: GT39, Female, India, age of onset is 14 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)

Case17: GT08, Male, India, age of onset is 8 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

Case32: GT50, Male, India, age of onset is 2 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)

Case21: GT17, 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.652C>T , (p.His218Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023445

gnomAD: N/A

Case12: GT41, Male, 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: NM_000419.3:c.727del (p.Leu243PhefsTer62)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940727

gnomAD: N/A

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

PMID: 16343278

Gene: ITGA2B and/or ITGB3

HGNC: 6138 and 6156

InsufficientEvidence: This article mentions a 4 year old with acquired thrombasthenia; however, no variants in ITGA2B and/or ITGB3 are mentioned therefore there is insufficient evidence

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

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

PMID: 29675921

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156, respectively as gene names shown above

Supplementary Tables 1 and 2 combined information:

Case15b: Male, 9 years old, brother to GT15a

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Available per Table 1, brother to GT15a

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 10-20% of αIIbβ3 expression measured by flow cytometry

PlateletAggregation: Platelet aggregation showed a small 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: ITGB3

Variant: NM_000212.2:c.1525del (p.Gln509Argfs*160) and NM_000212.2:c.1199G>A (p.Cys400Tyr)

LegacyVariant: N/A

ClinVar: 13562 (p.Cys400Tyr)

CAiD: CA915940237 (p.Gln509Argfs*160) and CA123244 (p.Cys400Tyr)

gnomAD: N/A

Case34: Patient LD

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 30% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.847del and NM_000212.2:c.863T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940765 and CA400024958

gnomAD: N/A

PreviouslyPublished: Reference 56

PMID: 9215749

Gene: ITGA2B and ITGB3

HGNC: 6138 abd 6156

Case24: Pakistan

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

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

PreviouslyPublished: Reference number 28

PreviouslyPublished: PMID: 1317725

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: https://glanzmann.mcw.edu/

Case5: Patient FLD (found in the GT database) gender and age are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0031364, HP:0006298

(Epistaxis, Ecchymosis, Prolonged bleeding after tooth extraction)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 2-5% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.818G>A (p.Gly273Asp)

LegacyVariant: (p.Gly242Asp)

ClinVar: 2894

CAiD: CA115837

gnomAD: N/A

PreviouslyPublished: 8282784

Case26: Patient NR

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000978

(Epistaxis, gingival bleeding, bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: N/A

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.433G>T (p.Asp145Tyr)

LegacyVariant: N/A

ClinVar: 13554

CAiD: CA123226

gnomAD: N/A

PreviouslyPublished: Ref 43

Case27: Patient BL

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0000225

(Bruising, epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 30% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.563C>T (p.Ser188Leu)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622981

gnomAD: MAF in the European non Finnish population is 0.000008793 https://gnomad.broadinstitute.org/variant/17-45362010-C-T

PreviouslyPublished: Reference 44

Case35: Patient Chinese 20 (found in GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000132, HP:0000979, HP:0000967

(Epistaxis, menorrhagia, purpura/petechiae)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: <15% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NM_000212.2:c.1199G>A (Cys400Tyr)

LegacyVariant: N/A

ClinVar: 13562

CAiD: CA123244

gnomAD: N/A

PreviouslyPublished: References 57 and 58

Case40: Patient P

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 44% GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGB3

Variant: NC_000017.11:g.47310169T>C

LegacyVariant: N/A

ClinVar: 13556

CAiD: CA123230

gnomAD: N/A

PreviouslyPublished: References 63-65

Case7: Patient KJ (can be 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, prolonged bleeding after dental 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.1073G>A (p.Arg358His)

LegacyVariant: N/A

ClinVar: 2896

CAiD: CA115839

gnomAD: N/A

PreviouslyPublished: Reference 18 in this article

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%.

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

Case#: 40, female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000790, HP:0000967, HP:0000978, HP:0004406, HP:0000225, HP:0006298, HP:0001892, HP:0002239, HP:0000132

Hematuria, Petechiae, Bruising susceptibility, Spontaneous, recurrent epistaxis, Gingival bleeding, Prolonged bleeding after dental extraction, Abnormal bleeding, Gastrointestinal hemorrhage, Menorrhagia

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

ClinVar: 1330321****

CAID: CA923726221 *

Variant: NM_000212.3:c.756del **

* Predicated different Amino Acid affected by Allele Registry according to this table it is Isoleucine but allele registry shows methionine to cysteine with frameshift

GnomAD: Not found

ExpressionEvidence:Flow Cytometry of platelet integrin: 1.2% B3 expression, 45.2% A2B expression

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

Case#: 29 year old, female

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: CA399802403

ClinVar: 1330318

Variant: NM_000419.5:c.1622T>A

Allele 2:

ClinVar: 2892

CAID: CA115834

Variant: NM_000419.5:c.1750C>T

GnomAD: East Asian Population 0.0002176 (4/18386)

ExpressionEvidence: Flow Cytometry of platelet integrin: .77% B3 expression, .37% A2B expression

Case#: 13, male

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, 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: 1330339

CAID: CA400024922

Variant: NM_000212.3:c.856G>A

GnomAD: Not Found

Allele 2

ClinVar: 1330314

CAID: CA400028591

Variant: NM_000212.3:c.1288C>T

GnomAD: Highest in European non-Finnish population 0.000008801 (1/113622)

ExpressionEvidence: Flow Cytometry of platelet integrin: 8.3% B3 expression, 88.8% A2B expression

Case#: 21 Female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0004406, HP:0000225, HP:0006298, HP:0001892

Petechiae, Bruising susceptibility, Spontaneous, recurrent epistaxis, Gingival bleeding, Prolonged bleeding after dental extraction, Abnormal bleeding

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

ClinVar: 953041

CAID:CA8623377

Variant: NM_000212.3:c.1913+5G>T

GnomAD: Highest in East Asian population (0.0001633) 3/18372

ExpressionEvidence:Flow Cytometry of platelet integrin: .5% B3 expression, 1.5% A2B expression

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

Case23: Patient CG, 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

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

Case4: Patient ZM, 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.693dup

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940315

gnomAD: N/A

Case11: Patient LF, 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

Case22: Patient DOM, 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: 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

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:

Case59: GT61, Female, 49 years old, French/Italian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000132

(Easy bruising, menorrhagia)

CaseHPOFreeText: 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: ITGB3

Variant: NM_000212.2:c.224del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622899

gnomAD: MAF in the European (non-Finnish) population is 0.000008795 https://gnomad.broadinstitute.org/variant/17-45360777-TG-T

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:

Case32: GT35b, Female, 16 years old, USA

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected sister who is 35a in this study (See Supplementary Table S1)

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 and ITGB3

Variant: ITGB3: NM_000212.2:c.392G>C (p.Arg131Pro) and NM_000212.2:c.777+1G>A ITGA2B: NM_000419.3:c.2264G>A (p.Arg755Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8622954, CA8623036, CA8602771

gnomAD: MAF in the African population is 0.00006152 http://gnomad.broadinstitute.org/variant/17-45361839-G-C, MAF in the Latino population is 0.0006774 http://gnomad.broadinstitute.org/variant/17-45363789-G-A, MAF in the Latino population is 0.0001903 http://gnomad.broadinstitute.org/variant/17-42454380-C-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case5: GT6, Female, 19, French/Algerian

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978 and HP:0000225

(Easy bruising, gingival bleeding)

CaseHPOFreeText: Severe bleeding

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed <5% expression of αIIbβ3

PlateletAggregation: Absent platelet aggregation (See Supplementary Table 1)

CasePreviousTesting: Sanger sequencing of ITGA2B and ITGB3

Gene: ITGB3

Variant: NM_000212.2:c.940G>T (p.Asl314Tyr)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400025612

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

Supplementary Table S1 & S2 Proband and Variant Information:

Case29: GT33b, Female, age not specified, USA/Laos

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother who is proband 33a in this article

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0002239

(Epistaxis, GI bleeding)

CaseHPOFreeText: Life-threatening bleeding at onset of menses

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: ITGB3

Variant: NM_000212.2:c.262C>T (p.Arg88Ter) and NM_000212.2:c.2113del (p.Leu705Cysfs*4)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400020703 and CA8623443

gnomAD: MAF in the Other population is 0.0001385 http://gnomad.broadinstitute.org/variant/17-45360816-C-T and MAF in the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Table S1 & S2 Proband and Variant Information:

Case3: GT4, Male, 6, French (Gypsy)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000967, HP:0001945 HP:0002719

(Petechiae, fever, infections, recurrent infections)

CaseHPOFreeText: Severe bleeding, hematomas since childbirth

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry showed 50% expression of αIIbβ3 and no binding of PAC-1 after activation (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:

Case18: GT21, Female, 61, French

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.1440-13_1440-1del (p.Arg480Serfs*106) and NM_000419.3:c.2864T>A (p.Leu955Gln)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA913184940 and CA399791171

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case63: GT66, Female, 15 years old, French/Ko

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected cousin (this is all the information we are provided with)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000175, HP:0000225, HP:0000421, HP:0031364

(Cleft palate, gingival bleeding, epistaxis, ecchymosis)

CaseHPOFreeText: Hematomas

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.1879-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case67: GT70, Female, 21 years old, French/Arab

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0002239, HP:0000421, HP:0000132

(Bruising, purpura, GI bleeding, epistaxis, menorrhagia)

CaseHPOFreeText: Hematomas, oropharynx 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: ITGB3

Variant: NM_000212.2:c.613_614+2del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940309

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case43: GT43a, Female, 7 years old, Moroccan (this proband died from epistaxis-see Supp Table S1)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Affected brother is 43b (See Supplementary Table S1)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421

(Severe epistaxis)

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: ITGB3

Variant: NM_000212.2:c.614+1G>T and NM_000212.2:c.683G>A (p.Arg228His)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023344 and CA8623025

gnomAD: MAF in the African population is 0.00008012 http://gnomad.broadinstitute.org/variant/17-45363694-G-A

Supplementary Table S1 & S2 Proband and Variant Information:

Case39: GT40, Female, 17 years old, Pankistani

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0030140

(Epistaxis, bleeding from mouth)

CaseHPOFreeText: Heavy bleeding at menarche

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.857T>A (p.Val286Asp)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805011

gnomAD: N/A

Supplementary Table S1 & S2 Proband and Variant Information:

Case50: GT50, Male, 78 years old, French

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0031364, HP:0000225

(Ecchymosis, gingival bleeding)

CaseHPOFreeText: Moderate bleeding syndrome

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: ITGB3

Variant: NM_000212.2:c.1260G>A (p.Lys376_Thr420del)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623200

gnomAD: MAF in the African population is 0.00004005 http://gnomad.broadinstitute.org/variant/17-45368454-G-A

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

Case29: (GT-34) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT31-GT34 are related

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding severity: Information not available for this proband (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 the East Asian population is 0.0001087 http://gnomad.broadinstitute.org/variant/17-45380183-TC-T

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

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

Case20: (GT-22) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Proband GT-22 is related to GT-21 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: ITGB3

Variant: NM_000212.2:c.2302-1G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034626

gnomAD: N/A

Case49: (GT-60) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

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

PMID: 30792900

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156 respectively as shown above

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

Case05: (GT-05) Male, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands 1-9 are related to GT-05 see Table 1

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

CasePresentingHPOs: Bleeding severity: Mild (See Supplementary Table 3)

CaseHPOFreeText: N/A

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

Case48: (GT-59) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

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

Case15: (GT-17) Female, age or ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Probands GT15-GT20 are related to GT-17 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: ITGB3

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

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400023600

gnomAD: N/A

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

PMID: 11798398

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

PMID: 20020534

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

Case4: (Proband CabGT-4), 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 surface expression as 53% GPIIb and 66% GPIIIa

Platelet Aggregation: N/A

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

Gene: ITGA2B

Variant: c.1442-13_1442-1del (This variant does not show up in the CAR or ClinVar)

LegacyVariant: N/A

ClinVar: N/A

CAiD: N/A

gnomAD N/A

Case18: (Proband CabGT-18), Gender, age and ethnicity were not specified

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.2944G>A (p.Val982Met) and NM_000419.3:c.2965G>A (p.Ala989Thr)

LegacyVariant: N/A

ClinVar: 381747 (p.Val982Met) and 417951 (p.Ala989Thr)

CAiD: CA16608466 (p.Val982Met) and CA8602498 (p.Ala989Thr)

gnomAD MAF in the European (non-Finnish) population is 0.00006486 https://gnomad.broadinstitute.org/variant/17-42451838-C-T and MAF in the Other popeulation for (p.Ala989Thr) is 0.001939 https://gnomad.broadinstitute.org/variant/17-42451817-C-T

Case13: (Proband CabGT-13) Male, age not specified, Japanese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

ProteinExpression: Flow cytometry showed <5% of GPIIIa and GPIIb 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.2333A>C (p.Gln778Pro)

LegacyVariant: N/A

ClinVar: 225393

CAiD: CA290947544

gnomAD MAF in the East Asian population is 0.0001087 https://gnomad.broadinstitute.org/variant/17-42453691-T-G

Supplementary Table S1:

Case62: GT73, 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: ITGB3

Variant: NM_000212.2:c.889G>A (p.Gly297Arg)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA8623074

gnomAD: MAF in the European (non-Finnish) population is 0.00002643 https://gnomad.broadinstitute.org/variant/17-45364547-G-A

Supplementary Table S1:

Case44: GT51, French/African, 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: ITGB3

Variant: NM_000212.2:c.861del (p.Arg287SerfsTer34) and NM_000212.2:c.1456del (p.Cys486A;afsTer183)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940375 and CA915940376

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

Supplementary Table S1:

Case64: GT75, French/African, 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.*165T>C

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940530

gnomAD: N/A

Supplementary Table S1:

Case33: GT39a, Sweden, gender and ethnicity 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.1882C>T (p.Arg628Ter)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399801310

gnomAD: MAF in the Latino population is 0.00003983 https://gnomad.broadinstitute.org/variant/17-42456075-G-A

Supplementary Table S1:

Case56: GT66, French/Korean, age and gender are not specified here

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.1879-2A>G

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290949031

gnomAD: N/A

Supplementary Table S1:

Case38: GT44, French, 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.1357C>T (p.Arg453Ter)

LegacyVariant: N/A

ClinVar: 631773

CAiD: CA399803529

gnomAD: N/A

Supplementary Table S1:

Case54: GT64, French, age and gender 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.257T>C (p.Leu86Pro) and NM_000419.3:c.1440-13_1440-1del (p.Arg480SerfsTer106)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290956162 and CA913184940

gnomAD: N/A

Supplementary Table S1:

Case7: GT8, 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.2348+5G>C

LegacyVariant:

ClinVar: N/A

CAiD: CA290947484

gnomAD: N/A

Supplementary Table S1:

Case50: GT58, Argentinian/European, 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.601G>A (p.Gly201Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399805612

gnomAD: N/A

Supplementary Table S1:

Case61: GT72, French, age and ethnicity 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.2951C>A (p.Thr984Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA399790180

gnomAD: N/A

PMID: 22210999

Gene: ITGA2B

HGNC: 6138

InsufficientEvidence: This article mentions a variant in ITGA2B; however, it is examined in a horse not human

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

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

PMID: 21113249

Gene: ITGA2B and ITGB3

HGNC: 6138 and 6156

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

Case22: Patient YF, 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: ITGB3

Variant: NM_000212.2:c.1550del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA626684864

gnomAD: MAF in the European (non-Finnish) population is 0.000008850 https://gnomad.broadinstitute.org/variant/17-45369791-AG-A

Case7: Patient HA, 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.1878G>C

LegacyVariant: N/A

ClinVar: 2903

CAiD: CA115852

gnomAD: N/A

Case11: Patient WV, 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: c.2232Gins (Noting this as an Unknown Variant as this won't show up in CAR-- I am sure there is a way to retrieve the CAiD; however, will need to discuss with senior biorcurator)

LegacyVariant: ^

ClinVar: ^

CAiD: ^

gnomAD: ^

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

Case7: Patient M7, Female, 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

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

Case29: (GT11) 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: ITGB3

Variant: NM_000212.2:c.2217del

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940690

gnomAD N/A

Case19: (GT53) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has a sister who does not have either of the 2 mutations (normal)

ParentalGenotype: Father: Does not have the Asp139His mutation but is heterozygous for the Tyr141Cys mutation. Mother: Heterozygous for the Asp139His mutation and is normal or does not harbor the Tyr141Cys 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: ITGB3

Variant: NG_008332.2:g.35655G>C (p.Asp139His) and NM_000212.2:c.422A>G (p.Tyr141Cys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400021843 and CA40002188, respectively as shown above

gnomAD N/A

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

Case36: (GT19) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: One brother is homozygous for the mutation and the other brother is heterozygous for the mutation

ParentalGenotype: Mother and father are heterozygous for 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: ITGA2B

Variant: There seems to be a typo in this variant, asked Shruthi NM_000419.3:c.937G>A

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA290954329

gnomAD MAF in the European (non-Finnish) population is 0.000008888 https://gnomad.broadinstitute.org/variant/17-42461461-C-T

Case32: (GT59) Gender, age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has one normal borther and one brother who is heterozygous for the mutation

ParentalGenotype: Both parents are heterozygous for this mutation that the proband harbors

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: ITGB3

Variant: NM_000212.2:c.155_156delinsTT

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940691

gnomAD N/A

Case18: (GT3) Gender, age and ethnicity are not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Has one brother and sister without the mutation and has one brother that is heterozygous for the variant

ParentalGenotype: Mother and father are both heterozygous for 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: ITGB3

Variant: NM_000212.2:c.2315T>C (p.Leu772Pro)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400034691

gnomAD MAF in the African population is 0.00006152 https://gnomad.broadinstitute.org/variant/17-45387518-T-C