Splicing and missense mutations in the human FXIIIA gene causing FXIII deficiency: effects of these mutations on FXIIIA RNA processing and protein structure

We have investigated the molecular basis of factor XIII (FXIII) deficiency in a family from the north-west region of the U.K. and identified two sequence changes in the FXIII subunit A (FXIIIA) gene, We report a novel Asn to Lys mutation at codon 541, and a g --> a mutation at the intron 5/exon 6 splice junction in the FXIIIA gene, The splicing mutation results in two abnormal FXIIIA transcripts. The Asn541 residue is important for stabilizing an external fold in the FXIIIA barrel 1 domain. The Asn541Lys mutation is expected to result in inappropriate folding and therefore an unstable FXIIIA molecule.