title: Spectrum of factor XI (F11) mutations in the UK population--116 index cases and 140 mutations.
abstract: Factor XI deficiency is an autosomal bleeding disorder of variable severity. It is particularly common in the Ashkenazi Jewish population, the result of two founder mutations - E117X and F283L. Recent studies have shown the causative mutations of Factor XI deficiency, outside the Ashkenazi Jewish population, to be highly heterogeneous. We have studied 116 index cases, mostly from an ethnically diverse UK population, in order to better understand the spectrum of mutations responsible for factor XI deficiency. A total of 140 causative mutations of the F11 gene were identified in 109 patients. Fifty-five (39.3%) of the mutations were one of three common mutations--E117X (Type II), F283L (Type III), or C128X. The remaining 85 (60.7%) mutations comprised at least 57 variants including 31 novel mutations and whole gene deletions. This large study reconfirms that, despite the presence of founder mutations in discrete populations, factor XI deficiency remains a highly heterogeneous disease at the molecular level. .
authors.affiliation: Centre for Haemostasis and Thrombosis, St. Thomas' Hospital, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Mitchell
authors.forename: Roger
authors.initials: R
authors.lastname: Mountford
authors.forename: Rachel
authors.initials: R
authors.lastname: Butler
authors.forename: Anwar
authors.initials: A
authors.lastname: Alhaq
authors.forename: Letian
authors.initials: L
authors.lastname: Dai
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Savidge
authors.forename: Paula H B
authors.initials: PH
authors.lastname: Bolton-Maggs
mesh_terms: D005172:Factor XI / Q000235:genetics*; D005173:Factor XI Deficiency / Q000175:diagnosis / Q000235:genetics*; D018703:Founder Effect; D017353:Gene Deletion; D018740:Genetic Heterogeneity; D006801:Humans; D009154:Mutation; D006113:United Kingdom
chemical_list: D005172:Factor XI