Phenotypic and genetic analysis of a pedigree affected with hereditary FV deficiency due to a novel deletional variant of F5 gene

Objective To analyze the phenotype and F5 gene variant in a pedigree affected with hereditary coagulation factor Ⅴ (FⅤ) deficiency. Methods All of the exons, flanking sequences, and 5′ and 3′ untranslated regions of the F5 gene were subjected to PCR and direct sequencing. Suspected variant sites were confirmed by clone sequencing. Influence of the variants was predicted by using software including ClustalX and Mutation Taster. Results The prothrombin time (PT) and activated partial thromboplastin time (APTT) of the proband were prolonged to 20.3 s and 59.2 s, respectively, while FⅤ activity (FⅤ∶C) and FⅤ antigen (FⅤ∶Ag) were reduced by 13% and 17%, respectively. The FⅤ∶C and FⅤ∶Ag of his father, sister and daughter were decreased to 35%, 37%, 29% and 42%, 46%, 35%, respectively. The proband was found to carry a heterozygous c. 2851delT variant in exon 13 of the F5 gene, which caused a frameshift and resulted in a truncated protein (p.Ser923LeufsX8). In addition, a heterozygous c. 1538G>A (p.Arg485Lys) variant was found in exon 10. The father, sister and daughter of the proband all carried the p. Ser923LeufsX8 variant, while his mother and son carried the heterozygous p. Arg485Lys polymorphism. His younger brother and wife were of the wild type. Bioinformatic analysis showed that p. Ser923 was highly conserved across various species. Mutation Taster scored 1.00 for the p. Ser923LeufsX8 variant, and the result has predicted a corresponding disease. Conclusion A heterozygous deletional mutation c. 2851delT in exon 13 of the F5 gene and a heterozygous c. 1538G>A polymorphism harbored by the proband may be associated with the decreased FⅤ level in this pedigree. Key words: Coagulation factor Ⅴ deficiency; Bioinformatics; F5 gene; Gene variant