Case#: Male, 20

DiseaseAssertion: Glanzmann thrombasthenia–like syndrome

FamilyInfo: Twin brother (shares variant), Mother, Figure 1B

ParentalGenotype: Maternal inheritence, diagnosed GTLS

CasePresentingHPOs: thrombocytopenia (HP:0001873), Platelet anisocytosis (HP:0032438), (HP:0003645) activated partial thromboplastin times, (HP:0000967) petechia

PlateletAggregation: Thrombocytopenia (51×109/L, reference interval (RI): 150–450×109/L), Serum antiplatelet antibody test was negative. Platelet macrocytosis.

CaseHPOFreeText: Occasional petechia noted. Platelet macrocytosis.

CaseNotHPOs: (HP:0012200) prothrombin, (HP:0001892) abnormal bleeding

CaseNotHPOFreeText: Platlets in Figure 1A. No thrombotic symptoms.

ProteinExpression: this mutation entails the substitution of the hydrophobic leucine with a hydrophilic arginine. This charge reversal in the TMD of β3 may potentially impact helix conformation, integrin assembly, and signaling pathways.Platelet aggregation was severely diminished in response to adenosine 5′-diphosphate, collagen, arachidonic acid, and epinephrine, but not ristocetin, Figure 1E. Flow cytometry showed slightly increased CD41a expression, probably because of increased platelet size, Figure 1F.

CasePreviousTesting: Exome sequencing via TruSight One expanded panel (Illumina), whole-genome sequencing via the Korean National Project of Bio Big Data, Maternal inheritance was confirmed via Sanger sequencing analysis.

PreviouslyPublished: NA

Gene: ITGB3

Variant: NM_000212.3: c.2192T>G, [NP_000203.2:p.Leu731Arg]

HGVS: NM_000212.3:c.2192T>G (ITGB3)

ClinVar: Absent

CAID: CA400034083

gnomAD: Absent