Molecular Basis of Inherited Factor XIII- A Deficiency among Patients from Sistan - Baluchestan

Background : Factor ХШ, the last zymogene in the clotting cascade, converts the loose fibrin polymer into a firm polymer. In the absence of factor ХШ the abnormal fibrin is soluble in acetic acid, as well as 5M urea. Factor ХШ is composed of 2 catalytic A subunit bounds and 2 B subunits as carriers (A2B2). The gene of A chain is located on chromosome 6. Factor ХШ deficiency is rare with a prevalence of only 1 in 2 million in the general population. The overwhelming majority of cases are due to mutations in subunit A. The aim of this study was to detect the mutations of subunit A.

  Materials & m ethods: In this study we investigated the molecular basis of inherited factor ХШ deficiency among 10 unrelated patients from Sistan and Balouchestan province in 2006. Mutations were detected by amplifying each exon. Those exons exhibiting the presence of heteroduplex by conformation sensitive gel electrophoresis (CSGE) were selected for direct sequencing. Sequencing of mutations was carried out by restriction fragment length polymorphism (RFLP).

  Results : All patients had homologous subsitiation of TGG to CGG in exon 4 which led to change of arginine to tryptophan.

  Conclusion : The mutation found in this study was in the core domain of enzyme. It seems that the changs in electric charge and affinity of enzyme to substrate‚as a result decreases the level of factor XIII-A activity.