Factor VII Deficiency

Pattern of Inheritance

Congenital FVII deficiency follows an autosomal recessive pattern of inheritance.12 The FVII gene is located on the long arm of chromosome 13 and consists of 9 exons preceded by a promoter region, spanning approximately 12 kb near the telomere.13 Genes for two other vitamin K-dependent proteins, FX and PROZ, are located close to the FVII gene.

Variations in the sequence comprise gene polymorphisms and a wide range of mutations. Gene polymorphic sites associated with variations in FVII levels have been extensively studied. Their contribution to arterial thrombotic events, such as stroke, myocardial infarction, and peripheral arterial disease, is actively debated in scientific circles.14

Gene polymorphisms such as the intronic mutation IVS7, the 5F7 polymorphism and the 353Arg-Gln polymorphism, reduce FVII levels to different extents.15,16 These polymorphisms have been shown to lose their impact when associated with severe gene lesions such as null mutations, which are present in symptomatic FVII-deficient patients.8 The impact of these polymorphisms on other mutations needs further study, and may depend on the particular mutational mechanisms involved.

In 2005, Mariani and colleagues published the first comprehensive approach to study the molecular genetics of FVII involving a large cohort of patients.8 To date, more than 130 mutations within the FVII gene have been reported.17

For further information on registries for congenital FVII deficiency, see the Research section.