Portal de Periódicos da CAPES

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

1998; Wiley; Volume: 103; Issue: 2 Linguagem: Inglês

10.1046/j.1365-2141.1998.01017.x

1365-2141

Rashida Anwar, Louise Gallivan, K. Miloszewski, A.F. Markham,

Endoplasmic Reticulum Stress and Disease

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.