Case#: 3 month old male neonate

Disease: Glazmann's Thrombasthenia

CasePresentingHPOs: HP:0000967, HP:0007420, HP:0003010

Petechiae, Spontaneous hematomas, Prolonged bleeding time

PlateletAgreggation: Impaired in response to all stimuli including adenine diphosphate (2%), collagen (24%), arachidonic acid (13%), and epinephrine (13%). In contrast, platelet aggregation to ristocetine was almost normal (67%; lower limit of normal is 70%).

ExpressionEvidence: Flow Cytometry analysis showed reduced αIIbβ3 expression on patient platelets

FamilyInfo: Pedigree Figure 1. Homozygous HPA-1aa father and heterozygous HPA-1ab mother indicating that both HPA-1a alleles inherited to the GT son are defective carrying either Cys460Trp or Trp11Arg mutation.

GenotypingMethod:

Compound heterozygous:

Allele 1

ClinVar: 953012

CAID: CA400029369

Variant: NM_000212.3:c.1458C>G

GnomAD: Not Found

FunctionalEvidence: Flow cytometry analysis of wild-type (Cys460) and mutant (Trp460) expressed on HEK293 cells showed equal surface expression of αIIbβ3 and αvβ3. Immunoblotting analysis (Figure 2B) showed that the mutant β3 migrated slightly slower in comparison with wild-type β3 isoform, indicating that the disruption of one disulfide bond due to Cys460Trp mutation alters the secondary structure of integrin αIIbβ3. However, evidence that Csy460Trp mutation alters the binding of some mAbs against HPA-1a.

Allele 2:

ClinVar: 953028

CAID: CA291240306

Variant: NM_000212.3:c.31T>C

GnomAD: Not Found