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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
1   From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK
,
Louise Gallivan
1   From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK
,
Krzysztof J. A. Miloszewski
1   From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK
,
Alexander F. Markham
1   From the Molecular Medicine Unit, University of Leeds, Clinical Sciences Building, St James’s University Hospital, Leeds, UK
› InstitutsangabenWe 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.
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Publikationsverlauf

Received 11. August 1999

Accepted after resubmission 21. März 2000

Publikationsdatum:
11. Dezember 2017 (online)

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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
 

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