Genetic Diagnosis And Phenotype Of Hereditary F? Deficiency:Analysis Of 9 Patients

[objective] To investigate mutations of the coagulation factor VII(F7) gene and the clinical features in 9 patients with hereditary FVII deficiency.[Methods] FVII coagulation activity(FVII:C) and antigen(FVII:Ag) were assayed by one-stage clotting test and double-antibody sandwich ELISA(enzyme-linked immunosorbent assay, ELISA), respectively. Genomic DNA was extracted from peripheral blood of the proband and pedigree family members. All the exons and flanking sequences of FVII gene were amplified by polymerase chain reaction(PCR) and gene analysis was performed by direct sequencing.[Results] Ten different mutations were identified in 9 unrelated probands, including 3 splice site mutations and 7 miss sense mutations, three(p.Gly406(346)Asn?c.*64G>A?p.Ile213(153)Asn) of them were the first reported in literature. One patient had p.Tyr128(68)Cys homozygous mutation, FVII:C :0.8%, FVII:Ag :2.5%, with a clinical feature of severe bleeding. Five patients had double heterozygous mutations p.Thr241(181)Asn and p.Gly406(346)Asn?IVS1a+5G>A and p.His408(348)Gln?IVS5-1G>A and p.His408(348)Gln?c.*64G>A and p.Ile213(153)Asn?p.Cys389(329)Gly and p.His408(348)Gln) with FVII:C :1.2%?4.4%?1.0%?0.5% and 1.2%, respectively, and presenting clinical bleeding symptoms of varying severity. Three patients had mono-heterozygous mutation: p.Cys389(329)Gly?p.His408(348)Gln and p.Thr419(359)Met, FVII:C: 0.5%?8.3% and 9.4%, respectively. The first patient had a history of bleeding, last two had no significant bleeding.[Conclusion] Ten types of FVII gene mutations are identified in 9 unrelated probands with hereditary FVII deficiency, three of them are the first reported in literature. p.His408(348)Gln is the commonly seen mutation, and FVII:C has no significant correlation with phenotypes.