Factor XIII Deficiency Causing Mutation, Ser295Arg, in Exon 7 of the Factor XIIIA Gene

Rashida Anwar; Louise Gallivan; Krzysztof J. A. Miloszewski; Alexander F. Markham

doi:10.1055/s-0037-1614072

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2000; 84(04): 591-594
DOI: 10.1055/s-0037-1614072

Review Article

Schattauer GmbH

Factor XIII Deficiency Causing Mutation, Ser295Arg, in Exon 7 of the Factor XIIIA Gene

Rashida Anwar

¹From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK

,

Louise Gallivan

¹From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK

,

Krzysztof J. A. Miloszewski

¹From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK

,

Alexander F. Markham

¹From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK

› Author Affiliations

Abstract

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.

Key words

Factor XIII - transglutaminase - deficiency - missense mutation

Full Text

References

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