Genotype-phenotype analyses of Iranian patients with and without hemophilia B Leyden: A single-center study

Abstract Background There is a high prevalence of inherited bleeding disorders in Iran, such as hemophilia A (HA) and hemophilia B (HB). This study aimed to analyze the molecular and clinical profiles of patients with HB.Methods A single-center study was conducted among patients with severe HB between March 20, 2000, and June 31, 2023. The polymerase chain reaction (PCR) amplification was used for all of the major regions, such as the promoter, the exons, the adjacent intronic regions, and the untranslated regions of the F9 gene. Finally, Sanger sequencing was performed on the PCR products.Results A total of 111 HB patients (17 with HB Leyden and 94 without HB Leyden) were enrolled in this study. The median age of the patients at the time of diagnosis was 12 months (IQR: 6 months to 60 months). A family history of hemophilia was reported in 64 (57.7%) of patients. The most common bleeding manifestations were hemarthrosis, bruising, and oral cavity bleeding. Among 94 patients without HB Leyden, 59 (62.8%) had missense, 21 (22.3%) had nonsense, and 8 (8.5%) had frameshift mutations. Moreover, the most frequent mutation in HB Leyden was c.-17 A > G in this study. Finally, two novel mutations (c. -14 T > C and c. -56 T > A) were identified in the promotor region.Conclusion The results of this study confirm that HB is caused by a wide range of molecular defects in Iran. Thus, by knowing the genotypes and phenotypes, we would be able to stratify the patients which is important in terms of their management and outcome.