Coagulation factor XI: a database of mutations and polymorphisms associated with factor XI deficiency

Abstract

Hereditary factor XI deficiency is a rare bleeding disorder that is found worldwide. Rapidly increasing numbers of mutations and polymorphisms in various populations have been reported. However, the number of identified mutations given in recent literature and available databases is named to be not more than 35. We assumed that this is clearly too low and that to date no comprehensive survey of mutations associated with factor XI deficiency is available. To provide a complete database of mutations and polymorphisms associated with factor XI deficiency we collected all available data on hereditary factor XI deficiency from main biological and medical databases [http://ncbi.nlm.nih.gov/pubmed and http://ncbi.nlm.nih.gov/omim (OMIM reference 264900) and the Human Gene Mutation Database for F11 mutations http://uwcmml1s.uwcm.ac.uk/uwcm/mg/search/119891.html] as well as from contributions to international congresses. As of 8 June 2004 the number of reported causative mutations is 81, of which 12 have been described in unrelated individuals by more than one study group. For three frequently observed mutations [type II and type III mutations (Gln116Stop and Phe283Leu) and Cys38Arg] common founders have been described. Furthermore, 20 polymorphisms have been described in association with factor XI deficiency, three of which have been reported by two independent study groups. For the majority, allele frequencies have been published for in the Caucasian and/or Black population.

Factor XI Deficiency

“…unc.edu/isth/mutations-databases/FactorXI_2007.html, http://www.wienkav.at/kav/kar/texte_anzeigen.asp?ID¼ 7137, and http:www.factorxi.com. 1,61,62 The high allelic heterogeneity of FXI deficiency is highlighted by the even distribution of genetic defects throughout the gene; Fig. 1 shows the mutational spectrum of F11 as reconstructed by integrating the data from the different databases.…”

Identification of five novel mutations in the factor XI gene (F11) of patients with factor XI deficiency

“…About 80 mutations causing FXI deficiency have been reported (http://archive.uwcm.ac.uk/uwcm/mg/search/ 119891.html) [9]. Among them, four are referred to as Jewish mutations (type I-IV) [10,11].…”

Update on the physiology and pathology of factor IX activation by factor XIa

“…Approximately 150 other human factor XI gene mutations associated with factor XI deficiency have been identified [38,101–103]. Most are missense or nonsense mutations that result in failure of protein to be secreted from cells (crossreactive material negative mutations [CRM − ]).…”