Factor 5 mutation profile in German patients with homozygous and heterozygous factor V deficiency.

Coagulation factor V (FV) plays an important role in the blood coagulation cascade as part of the prothrombinase complex. FV deficiency is a rare autosomal recessive bleeding disorder with variable phenotypic expression. Thus, our study reports 39 patients with FV deficiency. In 36 cases, we were able to identify a causative mutation. Of these, 20 patients were heterozygous for the identified mutation, nine were homozygous, six were compound heterozygous and one proband was pseudohomozygous. In the remaining patients, no mutation was found. A total of 42 genetic alterations (of which 33 were uniquely different mutations), comprising 19 missense mutations, eight nonsense mutations, four small deletions and two splice site mutations, were identified by this study. Twenty-three of these were novel sequence variations not previously described in the literature. Interestingly, all changes found in exon 13 resulted in null alleles as either nonsense mutations or small deletions. The overall profile of these new mutations corresponds well with the data published in the F5 database. In those cases, where data were available, information on FV activity levels and/or bleeding history is given. Interestingly, some patients with mild FV deficiency (FV:C about 50% of normal) also exhibited bleeding episodes. Our data substantially contribute to the broadening and better understanding of the FV deficiency mutational spectrum. Identifying the molecular basis of mutations underlying this rare coagulation disorder will allow more insight into the mechanisms involved in the variable clinical phenotypes of patients with FV deficiency.