Molecular genetic diagnosis of Bernard-Soulier syndrome in Iranian patients: reporting three novel mutations.

Bernard-Soulier syndrome (BSS), a rare inherited platelet disorder, is characterized by macrothrombocytopenia, typically with mild to moderate thrombocytopenia, and abnormal expression of the GPIb-IX-V complex on the platelet surface. BSS is caused by missense, nonsense, and frameshift mutations in the GP1BA, GP1BB, and GP9 genes. This study aimed to characterize the mutations associated with BSS in Iranian patients. This study investigated eight patients diagnosed with BSS. The coding regions of three genes associated with BSS (GP1BA, GP1BB, and GP9) were subjected to polymerase chain reaction (PCR) amplification. Subsequently, Sanger sequencing was performed on the PCR fragments. Furthermore, in silico analyses were conducted to assess the significance of novel mutations. Six different disease-causing mutations were identified, three of which were novel variations. Sequencing of the GP9 gene revealed two novel frameshift deletions: c.151_154delGCCC and c.357delT. Variants identified in the GP1BB gene consisted of one known missense mutation (c.47 T > C) and a single-nucleotide deletion (c.390delC). In the GP1BA gene, we identified three cases with a c.624_625insT mutation and one case with a novel missense substitution (c.522 C>A). The identified diverse mutations highlight the genetic heterogeneity observed among the studied patients.