The Founder Effect? - FXIII Deficiency in Southeast Iran: A Molecular Study Report

Background: Congenital factor XIII (FXIII) deficiency is an extremely rare bleeding disorder (RBD) with different clinical coagulation disorders and great impacts on the perioperative patient outcome. Its prevalence in Southeast Iran is approximately ۴,۰۰۰ times higher than the worldwide prevalence, with Trp۱۸۷Arg (c.۵۵۹T> C) as the only causative mutation of FXIII deficiency (FXIIID) there. We investigated the founder effect of rs۱۷۴۲۹۲۴, rs۴۹۶۰۱۸۱, rs۳۷۷۸۳۶۰ and rs۴۱۴۲۲۹۰ using haplotype analysis to define the genetic phenomenon in this geographic region.Materials and Methods: In a case-control study, ۱۰ patients with FXIIID and ۱۰ healthy individuals were assessed. Initially, Trp۱۸۷Arg (c.۵۵۹T>C) mutation was assessed in all study populations using a PCR-RFLP technique, then haplotype analysis was performed by assessing rs۱۷۴۲۹۲۴, rs۴۹۶۰۱۸۱, rs۳۷۷۸۳۶۰, and rs۴۱۴۲۲۹۰ polymorphisms. Data were analyzed using a two-proportion z-test.Results: All patients were homozygote for Trp۱۸۷Arg (c.۵۵۹T>C), and this mutation was not observed in any form of homozygote or heterozygote in the control group. Polymorphisms in rs۱۷۴۲۹۲۴, rs۴۹۶۰۱۸۱, and rs۳۷۷۸۳۶ were homozygote (TT, GG, GG, respectively) and T, G, and G alleles distribution in cases and controls with significant difference (P<۰.۰۰۱, P<۰.۰۰۱, and P=۰.۰۱ respectively). Rs۴۱۴۲۲۹۰ polymorphism showed no significant difference between patients and controls (P=۰.۳). Two types of haplotypes were observed in the case group, and haplotype number ۱* was observed among ۹۰% of them, while not observed in the control group.Conclusion: It seems that founder effectors of haplotype number *۱ have more antiquity versus other haplotypes, and probably founder effect is responsible for this high prevalence of FXIIID in the southeast of Iran.