Case2: 6 year old, Female, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Case1 is sister of this proband. Additional family information found in table 1.

ParentalGenotype: Father: Heterozygous for the p.Cys549Ser variant and did not find the p.Gln254Lys variant. Mother: Did not find the p.Cys549Ser variant but she is heterozygous for the p.Gln254Lys variant.

CasePresentingHPOs: HP:0002248

CaseHPOFreeText: Upper gastrointestinal bleeding added up to five times at age 2.

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The expression of CD41 and CD61 was detected by platelet immunofluorescence test-flow cytometry. The expression of CD41 and CD61 of Case1 was remarkably lower than other family members (261.90 and 355.45 respectively).

CasePreviousTesting: DNA was isolated and ITGB3 and ITGA2B gene sequences were amplified by PCR with a high fidelity Taq Polymerase.

Gene: ITGB3

Variant: NM_000212.2:c.1646G>C (p.Cys549Ser), and NM_000212.2:c.760C>A (p.Gln254Lys)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA400030198 (p.Cys549Ser) and CA400023674 (p. Gln254Lys)

gnomAD: MAF: 0.00005453 (p.Cys549Ser) https://gnomad.broadinstitute.org/variant/17-45369890-G-C and MAF not available for (p.Gln254Lys)

Case1: 5 year old, Female, Chinese

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Case2 is the sister of this proband, additional family information found in Table 1

ParentalGenotype: Father: Did not find the p.Cys549Ser variant and is heterozygous for p.Leu705CysfsTer4 variant. Mother: Heterozygous for the p.Cys549Ser variant and did not find the p.Leu705CysfsTer4 variant.

CasePresentingHPOs: HP:0004406, HP:0000790

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOsFreeText: N/A

ProteinExpression: The expression of CD41 and CD61 was detected by platelet immunofluorescence test-flow cytometry. The expression of CD41 and CD61 of Case1 was remarkably lower than other family members (261.90 and 355.45 respectively).

CasePreviousTesting: DNA was isolated according to the manufacturer's instruction-- ITGA2B and ITGB3 gene sequences were amplified by PCR with a high fidelity TAQ Polymerase.

Gene: ITGB3

Variant: NM_000212.2:c.1646G>C (p.Cys549Ser), and NM_000212.2:c.2113del (p.Leu705CysfsTer4)

LegacyVariant: N/A

ClinVar: Not available for either of the two variants.

CAiD: CA400030198 (p.Cys549Ser), CA8623443 (p.Leu705CysfsTer4)

gnomAD: MAF: 0.00005453 (p.Cys549Ser) https://gnomad.broadinstitute.org/variant/17-45369890-G-C and MAF: 0.0001087 (p.Leu705CysfsTer4) https://gnomad.broadinstitute.org/variant/17-45380183-TC-T

Supplementary Tables 1 and 2 combined information:

Case38: GT38, Female, 23 years old

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not available per supplementary table 1

ParentalGenotype: Parents are not consanguineous, no other genotype information available

CasePresentingHPOs: HP:0000978, HP:0000979, HP:0031364, HP:0000132

(Bruising, purpura, ecchymosis, 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 and ITGB3

Variant: NM_000419.3:c.2613del in ITGA2B (p.Leu872Cysfs*38) and NM_000212.2:c.1646G>C in ITGB3 (p.Cys549Ser)

LegacyVariant: N/A

ClinVar: N/A

CAiD: CA915940594 (p.Leu872Cysfs*38) and CA400030198 (p.Cys549Ser)

gnomAD: MAF of (p.Cys549Ser) in the East Asian population: 0.00005453 https://gnomad.broadinstitute.org/variant/17-45369890-G-C