Factor XII deficiency: a clinical and molecular genetic study.

Factor XII deficiency is a rare inherited disorder caused by clotting factor XII (FXII, F12) deficiency. It is often asymptomatic but can have both thrombotic and haemorrhagic symptoms. The aim of this study was to describe the spectrum of F12 gene mutations in a Russian population and learn more about the relationship between F12 variants and clinical phenotypes. We obtained and analysed genetic and clinical data from 33 apparently unrelated patients with FXII plasma levels below 60% and genetic data from 26 healthy controls with no history of FXII deficiency. Forty mutant alleles and six different deleterious substitutions were identified. Of these substitutions, three were major in the Russian population (c.-62C > T, c.-57G > C and c.1532-1G > A, total frequency 92.5%) and the three others (p.615 del C, c.1180_1181delCA, and CD218 TAT- > CAT p.Tyr218His) were rare and novel in the world population. Eight patients with mild FXII deficiency were found to be homozygous for a hypomorphic variant of functional polymorphism C46T and have no other deleterious substitutions in the F12 gene. Contrary to data in the literature, our study showed that mild haemorrhagic manifestations are common among patients with FXII deficiency.