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Thromb Haemost 2000; 84(04): 591-594
DOI: 10.1055/s-0037-1614072
DOI: 10.1055/s-0037-1614072
Review Article
Factor XIII Deficiency Causing Mutation, Ser295Arg, in Exon 7 of the Factor XIIIA Gene
We would like to thank Professor S.E.V. Phillips and Dr C. H. Trinh for helpful discussions on the structural implications of the FXIII Arg295 mutant and assistance with preparation of Fig. 3. Research in our laboratories is supported by the NHS Executive, the Wellcome Trust, Yorkshire Cancer Research and The Royal Society.
Further Information
Publication History
Received
11 August 1999
Accepted after resubmission
21 March 2000
Publication Date:
11 December 2017 (online)
Summary
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 have analysed the molecular basis of factor XIII deficiency in two patients and their parents, who originate from the North of Pakistan. Four sequence changes were identified: an AGC→AGG (Ser→Arg) FXIII deficiency-causing mutation 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 modelling we predict that the Ser295Arg mutation would prevent the FXIIIA molecule from folding correctly and thus result in an unstable FXIIIA mutant polypeptide. The sequence changes −246G→A, −23T→C and −24C→T are normal polymorphisms. RT-PCR analysis demonstrates that the intronic sequence changes do not appear to affect the accuracy of FXIIIA RNA processing.
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