title: Splicing and missense mutations in the human FXIIIA gene causing FXIII deficiency: effects of these mutations on FXIIIA RNA processing and protein structure.
abstract: 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.
authors.affiliation: Molecular Medicine Unit, University of Leeds, St James's University Hospital.
authors.forename: R
authors.initials: R
authors.lastname: Anwar
authors.forename: L
authors.initials: L
authors.lastname: Gallivan
authors.forename: K J
authors.initials: KJ
authors.lastname: Miloszewski
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
mesh_terms: 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*
chemical_list: D012333:RNA, Messenger; D011503:Transglutaminases