Case6: (GT12) 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

Case3: Patient MU, gender age and ethnicity not specified

DiseaseAssertion: Glanzmann thrombasthenia type I

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: Bleeding symptoms were evaluated by examining available hospital records. Mild bleeders were defined as those who had minor symptoms, such as epistaxis or gum bleeds, and moderate bleeders suffered, in addition, from bleeding complications after surgery and trauma. Severe bleeders were defined as those with a history of spontaneous or life-threatening hemorrhages, such as gastrointestinal bleeding, or who had repeated episodes requiring platelet transfusion. See Table 1.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: See Table 6

PlateletAggregation: See Table 6

CasePreviousTesting: To ascertain the mutations, we sequenced the coding regions of the αIIb and β3 subunits including the exon/intron boundaries

Gene: ITGA2B

Variant: NM_000419.3:c.641T>C (p.Leu214Pro)

LegacyVariant: N/A

ClinVar: 2901

CAiD: CA115848

gnomAD: N/A

Case1: Female, 56 years old, Japanese

DiseaseAssertion: Glanzmann thrombasthenia (Diagnosed at 21 years of age)

FamilyInfo:

ParentalGenotype:

CasePresentingHPOs: HP:0004406, HP:0000225

(Recurrent epistaxis, gingival bleeding)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: Flow cytometry demonstrated significantly decreased expression of CD41 and CD61 to less than 20% of normal levels (See Figure 2)

PlateletAggregation: An in vitro assay revealed no platlet aggregation in response to agonists except ristocetin.

CasePreviousTesting: DNA sequencing analysis revealed compound heterozygous mutations confirming a diagnosis of Glanzmann thrombasthenia

Gene: ITGA2B

Variant: NM_000419.3:c.2602-3C>G and NM_000419.3:c.641T>C (p.Leu214Pro)

LegacyVariant: N/A

ClinVar: 2893 and 2901

CAiD: CA10575472 and CA115848

gnomAD: MAF in East Asian population 0.00006523 http://gnomad.broadinstitute.org/variant/17-42453087-G-C

Case4: Patient LW (found in GT database)

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: N/A

ParentalGenotype: N/A

CasePresentingHPOs: HP:0000978, HP:0000421, HP:0006298

(Bruising, Epistaxis, Prolonged bleeding after tooth extraction)

CaseHPOFreeText: Blood transfusions were needed

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: 12% of normal GPIIIa and GPIIb surface expression

PlateletAggregation: N/A

CasePreviousTesting: N/A

Gene: ITGA2B

Variant: NM_000419.3:c.641T>C (p.Lue214Pro)

LegacyVariant: (p.Leu183Pro)

ClinVar: 2901

CAiD: CA115848

gnomAD: N/A

PreviouslyPublished: References 14 and 15