Case1: Female, 22 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: See Fig 1

ParentalGenotype: The patient's parents revealed reduced concentrations of glycoprotein llb-Illa and were considered to be heterozygotes. See Fig 1

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000132, HP:0000978

(Severe epistaxis, gingival bleeding, menorrhagia, spontaneous bruising)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Platelets had much reduced alphaIIb3 when estimated by crossed immunoelectrophoresis

PlateletAggregation: Platelet aggregation was absent with ADP, arachidonic acid, and collagen.

CasePreviousTesting: Sequenced all exons and splice sites of ITGA2B and ITGB3

Gene: ITGA2B

Variant: NM_000419.3:c.1073G>A (p.Arg358His) and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: (p.Arg327His) and (p.Gly381Arg)

ClinVar: 2896 and 381748

CAiD: CA115839 and CA8603182

gnomAD: MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

PreviouslyPublished: PMID: 3762006 proband is mentioned in this article

Case#: 33 year old, female

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0000978, HP:0006298

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:

CAID: CA8603182

Variant: NM_000419.5:c.1234G>A

GnomAD: Latino 0.0001453 (5/34414)

ExpressionEvidence:Flow Cytometry of platelet integrin: 1.3% B3 expression, .3% A2B expression

Supplementary Tables 1 and 2 combined information:

Case19: GT19, Female, 32 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per Table 1.

ParentalGenotype: Parents are consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000790, HP:0000132

(Epistaxis, gingival bleeding, hematuria, menorrhagia)

CaseHPOFreeText: Post traumatic hemorrhage

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.1234G>A (p.Gly412Arg)

LegacyVariant: N/A

ClinVar: 381748

CAiD: CA8603182 (p.Gly412Arg)

gnomAD: MAF in Latino population: 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

Case#: Male, 62, Egyptian

DiseaseAssertion: GT with concurrent platelet CD36 deficiency (~1 in 100 million) and anti‐CD36 antibodies

CasePresentingHPOs: HP:0000421,Epistaxis. HP:0000978, Bruising susceptibility. HP:0000225, Gingival bleeding. HP:0001903, Anemia. HP:0001934, Persistent bleeding after trauma. HP:0001058, Poor wound healing. HP:0002573, Hematochezia. HP:0005261, Joint hemorrhage.

PlateletAggregation: See Table 1. Normal platelet count. Normal platelet size, modestly elevated mean platelet volume. Normal response to ristocetin.

ProteinExpression: Flow cytometry. GPIb/IX Expression 108% (range: 65-124%); GPIIb/IIIa expression 0% (range:65-124%).

Gene: ITGA2B

Variant: c.2148dup, p.Leu717Alafs3X

HGVS: NM_000419.5:c.2148dup

ClinVar: 627273

CAID: CA915940304

gnomAD: Absent

Variant: c.1234G>A, p.Gly412Arg

HGVS: NM_000419.5:c.1234G>A

ClinVar: 381748

CAID: CA8603182

gnomAD: 0.00003236, https://gnomad.broadinstitute.org/variant/chr17-44381038-C-T?dataset=gnomad_r4

Case7: Patient FO

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.2153dup and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: (p.Gly381Arg)

ClinVar: 381748

CAiD: CA913189170 and CA8603182

gnomAD MAF in the Latino population is 0.0001453 https://gnomad.broadinstitute.org/variant/17-42458406-C-T

Case1: Female, 48 years old, ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421, HP:0000225, HP:0000978, HP:0000132, HP:0006298, HP:0005261

(Epistaxis, gingival bleeding, easy bruising, menorrhagia, bleeding after tooth extraction, hemarthrosis

CaseHPOFreeText: Hemorrhage after surgery

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Platelet surface glycoprotein analysis by flow cytometry revealed a severe αIIbβ3 deficiency (Table 3 shows specific values)

PlateletAggregation: There was a failure of ADP, collagen and adrenalin to induce platelet aggregation, but ristocetin-induced platelet aggregation (RIPA) was normal

CasePreviousTesting: Integrin alphaIIb subunit gene (ITGA2B) sequencing showed that this proband was a compound heterozygote

Gene: ITGA2B

Variant: NM_000419.3:c.1214T>C (p.Ile405Thr) and NM_000419.3:c.1234G>A (p.Gly412Arg)

LegacyVariant: (p.Ile374Thr) (p.Gly381Arg)

ClinVar: 381748

CAiD: CA290950815 (p.Ile403Thr) and CA8603182 (p.Gly412Arg)

gnomAD: MAF in Latino population 0.0001453 http://gnomad.broadinstitute.org/variant/17-42458406-C-T