Complete Genotype and Clinical Phenotype of Hemophilia B: A Study on Iranian Patients

Background: Hemophilia B which refers to the deficiency or functional defect of factor IX (FIX) is typically an X-linked bleeding condition that arises from heterogeneous mutations of the FIX gene (F9). The number of hemophilia cases in Iran is considerable and currently, about 1118 Iranian patients are suffering from hemophilia B, although a small number of them underwent genetic investigations. Here we assessed molecular defects and also laboratory and clinical findings of 10 Iranian cases with hemophilia B. Materials and Methods: A total of 10 cases with hemophilia B were enrolled in the study. Patients were clinically examined by a hematologist and their previous medical documents were surveyed carefully. Routine coagulation tests and FIX activity and antigen assays were performed for the studied patients. Genotyping of F9 for identifying genetic mutations was conducted by the Sanger sequencing method following PCR amplification of the promoter region and all the eight exons of the F9 gene. Results: The mean age of patients was 4 years (9 months to 16 years) and consanguinity was reported in 80% of cases. Patients were commonly manifested by hematoma (90%), epistaxis (80%), and hemarthrosis (70%) and the severity of the disorder was severe (70%) or moderate (30%). In nine out of 10 patients a genetic defect in F9 gene we detected including three missense (c.304T>C, c.1007T>A, c.191G>A) and three nonsense mutations (c.892C>T, c.880C>T, c.1113C>A). Based on the FIX variant database (http://www.factorix.org), five mutations have been reported previously, but mutation c.1007T>A (p.Ile336Asn) seems to be a novel mutation. Conclusion: Our results indicated the heterogeneous molecular defects of hemophilia B in Iran, as recorded in the FIX mutation database. Moreover, no specific genotype-phenotype association was observed in studied subjects.