The reference OMIM entry for this protein is 234000

Factor xii deficiency
F12 deficiency
Hageman factor deficiency
Haf deficiency

A number sign (#) is used with this entry because the disorder can be caused by mutation in the F12 gene (610619).

CLINICAL FEATURES

This deficiency was usually discovered because of the practice in some hospitals of routinely performing whole blood clotting times before surgical operations (McCain et al., 1959). Ratnoff and Steinberg (1962) analyzed data on 55 cases in 37 families. Parental consanguinity was present in at least 2 instances. Some heterozygotes show partial deficiency of Hageman factor. The Japanese case reported by Miwa et al. (1968) had first-cousin parents. Egeberg (1970) described 4 Norwegian families with deficient factor XII (about half normal). Unlike the usual experience of no abnormality, they showed a slight to moderate bleeding tendency and a high incidence of cerebral apoplexy occurring at a relatively early age. Some of the patients had attacks of local edema, severe headache, abdominal pain, and various forms of allergy. Braulke et al. (1993) presented data suggesting that reduced levels of factor XII activity may be a risk factor for repeated spontaneous abortions. Gordon et al. (1981) showed that both the clot-promoting activity and the antigenic properties of Hageman factor are lower in Orientals than in American whites. Factor XII deficiency seemingly inherited as an autosomal dominant was reported by Bennett et al. (1972). The authors hypothesized that the gene could be allelic with that responsible for the autosomal recessive form. Superficial migratory thrombophlebitis (Samlaska et al., 1990) and leg ulcer (Goodnough et al., 1983; Lammle et al., 1991) have been documented as skin manifestations of factor XII deficiency. Sato-Matsumura et al. (2000) reported 2 individuals with factor XII deficiency presenting with livedo and painful leg ulcers who improved dramatically after anticoagulant therapy. They suggested that factor XII deficiency may lead to a hypercoagulative state in some individuals, predisposing them to painful ulcers and livedo. In a study of 150 consecutive patients with retinal vein occlusion (RVO) compared with age- and gender-matched controls, Kuhli et al. (2004) found that factor XII deficiency was highly prevalent in RVO patients 45 years of age or younger. By contrast, the prevalence of factor XII deficiency in RVO patients older than 45 years appeared similar to that seen in healthy individuals. Koster et al. (1994) and Girolami et al. (2004) concluded that severe (homozygous) factor XII deficiency is not a cause of deep-vein thrombosis. In a study of myocardial infarction and arterial thrombosis in severe (homozygous) factor XII deficiency, Girolami et al. (2005) likewise concluded that the role of the coagulation factor deficiency in the pathogenesis of arterial thrombosis is minor.

MAPPING

The F12 gene, site of defects resulting in factor XII deficiency, maps to chromosome 5q33-qter (Royle et al., 1988). Soria et al. (2002) conducted a genomewide linkage screen to localize genes that influence variation in F12 levels. Two loci were detected: one on chromosome 5 and another on chromosome 10 (lod scores 4.73 and 3.53, respectively). On chromosome 5, the peak lod score occurred in the 5q33-qter region, where the F12 gene is located. Addition of the 46C/T polymorphism (610619.0004) in the F12 gene increased the multipoint lod score to 10.21. A bivariate linkage analysis of F12 activity and thrombosis further improved the linkage signal (lod = 11.73) and provi ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 234000 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).