A novel heterozygous mutation flanking the fourth calcium-binding domain of the ITGA2B gene induces severe bleeding complications: a case report and literature review

Abstract

Glanzmann thrombasthenia is a rare autosomal recessive genetic disease characterized by platelet aggregation dysfunction caused by a congenital defect of platelet membrane glycoprotein IIb/IIIa (integrin αIIbβ3). Integrin αIIbβ3, a calcium-dependent heterodimer, plays a critical role in platelet aggregation. We described a boy who was hospitalized with serious epistaxis at 10 months of age who had a history of repeated petechiae and spontaneous epistaxis since birth. Flow cytometry showed normal surface expression of platelet antigens. Genetic analysis and sequencing revealed the novel missense mutation c.G1252>T (p.Gly418Cys) in ITGA2B. This heterozygous amino acid mutation flanked the fourth calcium-binding domain and may interfere with integrin biogenesis via mechanisms other than merely altering cell surface expression. We discuss the heterogeneity of the genotype and phenotype with this atypical case and review the relevant literature on mutations adjacent to or within the calcium-binding domains in Glanzmann thrombasthenia.