Case#: Case 2, 20 yo Female

DiseaseAssertion: Glanzman thrombasthenia

ParentalGenotype: Not provided

CasePresentingHPOs: (HP:0000978, Bruising susceptibility) (HP:0000421, Epistaxis)

PlateletAggregation: Strong reduction of platelet aggregation with all agonists, except ristocetin. Normal platelet count.

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

ProteinExpression: Flow cytometry, platelets with 18% to 24% residual αIIbβ3

CasePreviousTesting: Not provided

PreviouslyPublished: Not provided

Gene: ITGB3

HGVS: NM_000212.3:c.187C>T

ClinVar: 631774 https://www.ncbi.nlm.nih.gov/clinvar/variation/631774/

CAID: CA8622892

gnomAD: PopMax = 0.00002555 https://gnomad.broadinstitute.org/variant/17-47283375-C-T?dataset=gnomad_r4

Gene: ITGB3

HGVS: NM_000212.3:c.505C>T

ClinVar: 953061 https://www.ncbi.nlm.nih.gov/clinvar/variation/953061/

CAID: CA291224658

gnomAD: PopMax = 2.800e-7 https://gnomad.broadinstitute.org/variant/17-47284586-C-T?dataset=gnomad_r4

Case#: Patient 8

DiseaseAssertion: Glanzmann thrombasthenia

FamilyInfo: Not provided

ParentalGenotype: Not provided

CasePresentingHPOs: (HP:0000421, Epistaxis)

PlateletAggregation: All patients had abnormal platelet aggregation studies prompting analysis of platelet glycoprotein expression by flow cytometry.

ProteinExpression: Flow cytometry, 11 of 12 patients with GT had reduced antibody binding to GPIIb/IIIa

CasePreviousTesting: Not provided

PreviouslyPublished: Not provided

Gene: ITGA2B

Variant: c.1750C>T, p. (R584X)

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

ClinVar: 2892 https://www.ncbi.nlm.nih.gov/clinvar/variation/2892/

CAID: CA115834

gnomAD: PopMax = 0.00008834 https://gnomad.broadinstitute.org/variant/17-44380004-G-A?dataset=gnomad_r4

Variant: c.2671C>T, p. (Q891X)

HGVS: NM_000419.5:c.2671C>T

ClinVar: 953054 https://www.ncbi.nlm.nih.gov/clinvar/variation/953054/

CAID: CA8602626

gnomAD: PopMax = 0.000007390 https://gnomad.broadinstitute.org/variant/17-44375647-G-A?dataset=gnomad_r4

Case#: Female, at birth

DiseaseAssertion: Glanzmann Thrombasthenia

FamilyInfo: Figure 1 Consanguinity Mother: 27 yo. Positive for mutation. Epistaxis, hypochromic microcytic anemia, cesarean postoperative vaginal bleeding. Maternal aunt present with GT, Positive for mutation. Maternal cousin present with GT, Positive for mutation. Paternal cousins present with GT, Positive for mutation.

ParentalGenotype: Both parents heterozygous carriers.

CasePresentingHPOs: HP:0000978, Bruising susceptibility. HP:0000225, Gingival bleeding. HP:0003265, Neonatal hyperbilirubinemia. HP:0011869, Abnormal platelet function. HP:0004887, Respiratory failure requiring assisted ventilation. HP:0000967, Petechiae.

PlateletAggregation: Normal coagulation. Reduced platelet function.

CaseHPOFreeText: APGAR score 9. Spontaneous skin bruising. Started on feeds second day of life.

ProteinExpression: Platelet function assays showed severely reduced activity.

Gene: ITGB3

Variant: p.Asp145Asn

HGVS: NP_000203.2:p.Asp145Asn

ClinVar: 627066

CAID: CA400021939

gnomAD: Absent