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

Case1: Female, 3 years old, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A (No information about the family was available since the child was adopted)

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000421 (Epistaxis)

CaseHPOFreeText: Mucocutaneous hemorrhages, prolonged bleeding time

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

ProteinExpression: Protein expression was estimated by flow cytometry and western blot analysis. The analysis revealed less than 10% of surface expression of alphaIIbbeta3 relative to control platelets. (See Fig 2)

PlateletAggregation: Platelet aggregation in response to ADP, collagen, adrenaline, and arachidonic acid was less than 5% that of control platelets, and no clot retraction was observed. Ristocetin-induced platelet agglutination and plasma fibrinogen content were within the normal range.

CasePreviousTesting: Sequencing for mutations was carried out by direct sequencing of PCR overlapping fragments of reversed transcribed αIIb and β3 mRNA.

Gene: ITGA2B

Variant: NM_000419.3:c.2829C>T (p.Pro943Leu), NM_000419.3:c.2621T>G (p.Ile874Ser), NM_000419.3:c.1750C>T (p.Arg584Ter)

LegacyVariant: (p.Ile843Ser) and (p.Arg553Ter) and (p.Pro912Leu)

ClinVar: 2891, 2892

CAiD: CA500263536, CA115831, CA115834

gnomAD: MAF in the European (Finnish) population is 0.4395 https://gnomad.broadinstitute.org/variant/17-42453065-A-C and MAF in the East Asian population is 0.0002176 https://gnomad.broadinstitute.org/variant/17-42457372-G-A