Phenotypic and genotypic characterization of two factor VII deficiency patients from southeastern China

The congenital factor VII deficiency (FVIID) is a rare autosomal recessive haemorrhagic disease caused by mutations in the F7 gene. The aim of this study was to identify the mutations causing FVII deficiency and explain the genotype–phenotype association in two unrelated Chinese patients. Mutation detection was conducted by sequencing the whole F7 gene coding exons, exon–intron boundaries and the untranslated regions of 3′ and 5′. Then, the genetic information was analyzed to predict the structures of the mutated proteins. A total of four different mutations were detected, including three missense mutations (c.64G>A, c.286A>G, and c.722C>A, predicting p.Gly22Ser, p.Arg96Gly, p.Thr241Asn, respectively) and one insertion mutation (c.204_205insCGGC, predicting p. Leu68Argfs ∗ 37), among which two were reported for the first time (p.Arg96Gly, p.Leu68Argfs ∗ 37). Multiple sequence alignments of FVII protein revealed that the residues p.Arg96 and p.Thr241 were highly conserved. The novel missense mutation p.Arg96Gly was determined as damaging with online software Polyphen-2 and SIFT. We investigated two asymptomatic patients diagnosed with severe FVII deficiency and identified two novel mutations (the mutation p.Arg96Gly and p.Leu68Argfs ∗ 37). Identification of the F7 mutations was important for genetic counseling and accurate prediction of the inheritance pattern.