title: Molecular basis of inherited factor XIII deficiency: identification of multiple mutations provides insights into protein function.
abstract: Factor XIII (FXIII) is a zymogen essential for normal haemostasis. In inherited FXIII deficiency the majority of cases show absence of the FXIIIa subunit. Molecular analysis of PCR-amplified FXIIIa subunit exonic regions, and of RT-PCR amplified cDNA from six patients with FXIIIa subunit deficiency, from five unrelated families, has revealed 10 sequence changes: three mutations resulting in abnormal splicing of pre-mRNA, one nonsense mutation, one deletion/insertion change, three point mutations producing Val34Leu, Asn60Lys and Arg408Gln changes, and two silent mutations. In three families the patients are homozygous for a specific deficiency causing mutation, and patients from the remaining two families are compound heterozygotes. Understanding the molecular pathology of the disorder provides insights into the structure-function relationships of the various domains within the FXIII protein. From a clinical point of view, it enables direct diagnosis at the DNA level and may aid the development of FXIII analogues to promote wound healing.
authors.affiliation: Department of Medicine, University of Leeds, St James's University Hospital.
authors.forename: R
authors.initials: R
authors.lastname: Anwar
authors.forename: A D
authors.initials: AD
authors.lastname: Stewart
authors.forename: K J
authors.initials: KJ
authors.lastname: Miloszewski
authors.forename: M S
authors.initials: MS
authors.lastname: Losowsky
authors.forename: A F
authors.initials: AF
authors.lastname: Markham
mesh_terms: D001483:Base Sequence; D005177:Factor XIII Deficiency / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D017421:Sequence Analysis; D011503:Transglutaminases / Q000737:chemistry / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D011503:Transglutaminases