Factor XIII deficiency causing mutation, Ser295Arg, in exon 7 of the factor XIIIA gene

Inherited factor XIII (FXIII) deficiency is an autosomal recessive disorder which results in a serious bleeding diathesis, problems with wound healing and a very high risk of recurrent miscarriage in deficient females. We hav e analysed the molecular basis of factor XIII deficiency in two patients an d their parents, who originate from the North of Pakistan. four sequence ch anges were identified: an AGC-->AGG (Ser-->Arg) FXIII deficiency-causing mu tation in codon 295; G-->A at position -246 upstream of exon 1; T-->C and C -->T at positions -23 and -24, respectively, in intron 9. Using molecular m odelling we predict that the Ser295Arg mutation would prevent the: FXIIIA m olecule from folding correctly and thus result in an unstable FXIIIA mutant polypeptide. The sequence changes (-246)G-->A, T-23-->C and C-24-->T are n ormal polymorphisms. RT-PCR analysis demonstrates that the intronic sequenc e changes do not appear to affect the accuracy of FXIIIA RNA processing.