Profiling the mutational landscape of coagulation factor V deficiency

Coagulation factor V (FV) is a 330-kDa procofactor of the coagulation cascade that, upon activation, contributes to the formation of the prothrombinase complex, essential for the rapid generation of thrombin.1 FV deficiency (Online Mendelian Inheritance in Man #227400; https://www.omim.org/) is an autosomal recessive disorder, with an estimated prevalence in the general population of 1:1 million.2 The most common forms of FV deficiency are characterized by FV antigen (FV:Ag) levels that can vary from mildly reduced to unmeasurable (quantitative defect), whereas qualitative defects, showing normal/moderately decreased antigen levels associated with reduced FV coagulant activity (FV:C), are far rarer.2 Clinical manifestations range from mild bleedings (such as epistaxis, hematomas, easy bruising, and menorrhagia) to severe gastrointestinal or central nervous system hemorrhages.2 Both monoallelic and biallelic mutations in the FV gene (F5; 25 exons, 75 kb of length, chromosome 1q24.2) have been associated with FV quantitative defects, for a total of 139 mutations (Human Gene Mutation Database, public version, http://www.hgmd.cf.ac.uk/ac/index.php; accessed on April 05, 2019). Here, we present phenotype/genotype data on the largest cohort of FV deficient patients analyzed so far. In addition, integrating our results with the huge amount of data coming from F5-specific and genomic databases, we defined the mutational landscape of FV deficiency and estimated its world-wide prevalence