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Hum Mutat. 2016 Oct;37(10):1030-41. doi: 10.1002/humu.23041. Epub 2016 Aug 21.

Coagulation Factor XIIIA Subunit Missense Mutations Affect Structure and Function at the Various Steps of Factor XIII Action.

Author information

1
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
2
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. arijit.biswas@ukb.uni-bonn.de.
3
Paul Ehrlich Institut, Langen, Germany.
4
Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
5
Nees Institute for Biodiversity of Plants, University of Bonn, Bonn, Germany.
6
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany. johannes.oldenburg@ukb.uni-bonn.de.

Abstract

Inherited defects of coagulation Factor XIII (FXIII) can be categorized into severe and mild forms based on their genotype and phenotype. Heterozygous mutations occurring in F13A1 and F13B genes causing mild FXIII deficiency have been reported only in the last few years primarily because the mild FXIII deficiency patients are often asymptomatic unless exposed to some kind of a physical trauma. However, unlike mutations causing severe FXIII deficiency, many of these mutations have not been comprehensively characterized based on expression studies. In our current article, we have transiently expressed 16 previously reported missense mutations detected in the F13A1 gene of patients with mild FXIII deficiency and analyzed their respective expression phenotype. Complimentary to expression analysis, we have used in silico analysis to understand and explain some of the in vitro findings. The expression phenotype has been evaluated with a number of expression phenotype determining assays. We observe that the mutations influence different aspects of FXIII function and can be functionally categorized on the basis of their expression phenotype. We identified mutations which even in heterozygous form would have strong impact on the functional status of the protein (namely mutations p.Arg716Gly, p.Arg704Gln, p.Gln602Lys, p.Leu530Pro, p.His343Tyr, p.Pro290Arg, and p.Arg172Gln).

KEYWORDS:

F13A1; F13B; Factor XIII(FXIII)deficiency; expression analysis; in silico structural analysis; molecular basis of inherited coagulopathies

PMID:
27363989
DOI:
10.1002/humu.23041
[Indexed for MEDLINE]

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