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