Comparison of F13A1 gene mutations in 73 patients treated with recombinant FXIII-A2

Haemophilia : the Official Journal of the World Federation of Hemophilia
V IvaskeviciusJohannes Oldenburg

Abstract

Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder usually caused by mutations in the F13A1 gene that produce a severe quantitative (type I) deficiency of the FXIII-A subunit. To determine the genotypes of patients with severe FXIII-A deficiency treated with recombinant FXIII-A subunit (rFXIII-A2 ) participating in three international efficacy and safety trials. We determined the genotypes of 73 patients in total; 32 had already undergone genotype analysis and were known to carry F13A1 mutations that have been previously reported in the literature. Mutation screening was performed in 41 patients with unknown genetic status using direct sequencing. In total, 51 distinct mutations in 73 patients were identified. Two patients showed a phenotype of severe FXIII-A deficiency, despite having heterozygous missense mutations. Two siblings carried a missense mutation in the F13A1 gene (p.Ser296Arg) in combination with a novel, probably polymorphic variant of the F13B gene (p.Ser654Phe). Molecular modelling of five F13A1 novel missense mutations (p.Leu171Phe, p.Glu204Lys, p.Leu276Phe, p.Asp405His and p.Gly411Cys) predicted a damaging effect of these mutations on protein structure. Although five pat...Continue Reading

References

Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
May 1, 1980·Journal of Clinical Pathology·F Rodeghiero, T Barbui
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·V C YeeD C Teller
Aug 26, 1998·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·S AslamT Mandalaki
Feb 23, 1999·British Journal of Haematology·S KangsadalampaiP G Board
Feb 13, 2001·European Journal of Haematology·R AnwarA Markham
Mar 10, 2001·Haemophilia : the Official Journal of the World Federation of Hemophilia·J Di PaolaG Young
May 5, 2001·Genome Research·P C Ng, S Henikoff
Dec 26, 2003·Human Mutation·Flora PeyvandiPier Mannuccio Mannucci
Sep 11, 2004·Haemophilia : the Official Journal of the World Federation of Hemophilia·P H B Bolton-MaggsA D Mumford
Nov 25, 2006·Haemophilia : the Official Journal of the World Federation of Hemophilia·J Oldenburg, A Pavlova
Jun 6, 2007·Thrombosis and Haemostasis·Vytautas IvaskeviciusUNKNOWN Study Group
Apr 1, 2010·Nature Methods·Ivan A AdzhubeiShamil R Sunyaev
Jun 11, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·S ShanbhagK Ghosh
Aug 5, 2011·Haemophilia : the Official Journal of the World Federation of Hemophilia·G CastamanF Rodeghiero
Dec 18, 2013·Haemophilia : the Official Journal of the World Federation of Hemophilia·M BorhanyH P Kohler
Aug 8, 2015·Haemophilia : the Official Journal of the World Federation of Hemophilia·K PénzesG E Rivard
Aug 25, 2016·Seminars in Thrombosis and Hemostasis·Manuel CarcaoDiane Nugent

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Nov 9, 2018·Cold Spring Harbor Molecular Case Studies·Benjamin BriggsUNKNOWN RCIGM Investigators
Jul 28, 2020·Clinical Journal of Gastroenterology·Masaki MurataAkira Andoh
May 6, 2021·Clinical Journal of Gastroenterology·Masaki MurataShin'ichi Miyamoto

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