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.
Anwar
R
R
Molecular Medicine Unit, University of Leeds, St James's University Hospital.
Gallivan
L
L
Miloszewski
K J
KJ
Markham
A F
AF
D000328:Adult; D005177:Factor XIII Deficiency / Q000235:genetics*; D005260:Female; D006801:Humans; D020125:Mutation, Missense; D017354:Point Mutation; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D011503:Transglutaminases / Q000235:genetics*
D012333:RNA, Messenger; D011503:Transglutaminases