Bernard-Soulier syndrome caused by two novel heterozygous GP1BA gene mutations: a case report and literature review.

Background: Bernard-Soulier syndrome (BSS) is a rare inherited macrothrombocytopenia, usually autosomal recessive, which is characterized by prolonged bleeding, thrombocytopenia, and abnormally large platelets.

Methods: For more than 6 years, we misdiagnosed a patient with BSS without an obvious bleeding tendency as having idiopathic thrombocytopenia purpura (ITP), prior to obtaining a genetic analysis. On admission, routine hematology showed a platelet count of 30 × 10⁹/L and mean platelet volume (MPV) of 14.0 fL.

Results: Whole-exome sequencing revealed two likely pathogenic heterozygous mutations (c.95_101del and c.1012del) in GP1BA. Flow cytometry analysis of platelet membrane glycoproteins indicated that the expression of GP1b was 0.28% of the normal level. Platelet aggregation tests indicated that platelet aggregation was inhibited by ristocetin- (1.7%), ADP- (14.5%), and arachidonic acid- (5.6%) induced platelet aggregation. A literature review identified reports on 53 mutations in the GP1BA gene in 253 patients, 29 mutations in the GP1BB gene in 90 patients, and 32 mutations in the GP9 gene in 114 patients.

Conclusion: This case report describes two novel gene mutation sites that have not been reported previously, enriching understanding of the GP1BA mutation spectrum.