Recurrent Founder Variant in Inherited FVII Deficiency: Molecular Spectrum Analysis in Southeast China Recurrent Founder Variant in Inherited FVII Deficiency: Molecular Spectrum Analysis in Southeast China

Background Factor VII (FVII) deficiency is a rare congenital coagulation disorder inherited in an autosomal recessive manner, characterized by reduced plasma FVII levels. Several variants in the F7 gene have been identified across different populations, with higher prevalence in certain regions. However, limited reports exist on predominant variants in Chinese and East Asian populations, highlighting the need for this study to fill the gap and improve understanding of genotype-phenotype correlations. Result This study characterizes severe FVII deficiency in 85 unrelated Chinese families, 57 exhibited severe FVII defects. Notably, 31 out of 57 experienced various bleeding manifestations, with the most prevalent being gingival bleeding, epistaxis, and menorrhagia. The Pearson's rank correlation test yielded correlation coefficients of − .496 (P = .000), − .266 (P = .014), and .149 (P = .175) between FVII activity and PT, FVII activity and bleeding scores, and PT and bleeding scores, respectively. Direct sequencing of the exons of the F7 gene and its border regions was conducted on all patients. The five variants with the highest allele frequencies were p.Arg364Gln, p.His408Gln, p.Arg337Cys, p.Cys10Profs16, and p.Cys389Gly. The p.Arg364Gln variant was identified in 11 individuals with homozygotes and 6 with compound heterozygosity, with the highest allele frequency of 30.51%. The variants p.Gln160Leu, p.Leu170*, p.Ser329Pro, and p.Trp344Gly were previously identified and reported by our research group. Additionally, a novel variant, p.Ile421Serfs76, is reported for the first time. This study, representing one of the largest cohorts of FVII variants in China, suggests that the prevalence of FVII deficiency may be underestimated. This conclusion is supported by the high proportion of asymptomatic subjects found to have low FVII levels. Conclusion The findings of this study, which represents one of the largest cohorts of FVII variants in China, indicate that the prevalence of FVII deficiencies may be underestimated. This is due to the high proportion of asymptomatic individuals with low FVII:C levels. The significant association between FVII:C levels, prothrombin time, and bleeding symptoms highlights the necessity for continued genetic analysis to enhance our comprehension of genotype-phenotype correlations and to refine diagnostic and management strategies for FVII deficiency in the Chinese population.