Journal of

  Abstract

 Background and Objectives

 Factor ХШ is the last enzyme in the clotting cascade. The gene of A chain is located on chromosome 6. Deficiency of factor ХШ in autosomal recessive conditions occurs at a frequency of 1 in 2 million general population. The aim of this study was to detect the mutations of subunit A in both patients and carriers.

 Materials and Methods

 In this study we have investigated the molecular basis of inherited FХШ deficiency among patients from 21 unrelated Iranian families. Mutation were detected by amplifying each exon. Those exons exhibiting the presence of hetero duplex formation sensitive gel electrophoresis, were selected for direct sequencing. After sequencing, detected mutation was carried out by restriction fragment length polymorphism (RFLP).

 Results

 All patients having entered the study had mutations. Twelve patients had homologues substitution of TGG→CGG in exon 4, 1 insertion mutation occurring in exon 7 triple G, 2 patients demonstrated mutation exon 9 ATG→ AAG, 3 patients had substitution of CGG→ CAG in exon 10, and 3 patients showed a homologue subsituation mutation in exon 15 GCC→ GTC.

 Conclusions

 Our findings suggest that the activity of enzyme is highly dependent on the core domain. Changes in charge, amino acid tail and conformation lead to decreased enzyme activity. Also tetrameric structure is calcium related. It seems that changes of amino acid sequence convert enzyme stability.