Novel factor VII gene mutations in six families with hereditary coagulation factor VII deficiency. Issue 9 (2nd August 2021) - Zhang, Xiaoyu
Abstract: Introduction: Hereditary human coagulation factor VII (FVII) deficiency is an inherited autosomal recessive hemorrhagic disease involving mutations in the F7 gene. The sites and types of F7 mutations may influence the coagulation activities of plasma FVII (FVII: C) and severity of hemorrhage symptoms. However, the specific mutations that impact FVII activity are not completely known. Methods: We tested the coagulation functions and plasma activities of FVII in seven patients recruited from six families with hereditary FVII deficiency and sequenced the F7 gene of the patients and their families. Then, we analyzed the genetic information from the six families and predicted the structures of the mutated proteins. Results: In this study, we detected 11 F7 mutations, including four novel mutations, in which the mutations p.Phe84Ser and p.Gly156Cys encoded the Gla and EGF domains of FVII, respectively, while the mutation p.Ser339Leu encoded the recognition site of the enzymatic protein and maintained the conformation of the catalytic domain structure. Meanwhile, the mutation in the 5′ untranslated region (UTR) was closely associated with the mRNA regulatory sequence. Conclusion: We have identified novel genetic mutations and performed pedigree analysis that shed light on the pathogenesis of hereditary human coagulation FVII deficiency and may contribute to the development of treatments for this disease. Abstract : In this study, we performed coagulation index tests and gene sequencing on 7 hereditary FVII deficiency patients and their family members to explain the pathogenesis of the disease based on the analysis of their genetic information. Also, we compared the structures of newly discovered mutant proteins with the wild type and predicted their pathogenicity. To sum up, this study expands our insight on the pathogenesis of hereditary human coagulation FVII deficiency.