Recurrent mutations and genotype-phenotype correlations in hereditary factor VII deficiency in Korea

Coagulation factor VII (FVII) deficiency is a rare hereditary coagulopathy caused by mutations in the F7 gene. The aims of this study were to characterize the molecular defect of F7 in Korean patients with FVII deficiency and to find genotype-phenotype correlations. Study individuals consisted of 14 unrelated Korean patients with FVII deficiency with residual FVII activities ranging from 1 to 34%. To identify causative mutations, we performed PCR amplification and direct sequencing of all exons and flanking sequences of F7 gene. In all 14 patients, one (N=4) or two (N=10) mutant alleles were identified. A total of 11 unique mutations were detected, of which four were novel (c.-1C>T, p.V54RfsX53, p.R59_R60dupRR, and p.L314 V). Four recurrent mutations were observed in 86% of patients (12 of 14) (C389G, C115X, G343S, and c.572-1G>A) and accounted for 71% of all mutant alleles (17 of 24). The residual FVII activity was more than 5% in all six asymptomatic patients (21%, range 6-34%), whereas it was 5% or less in all eight symptomatic patients (2%, range 1-5%). In addition, the mean residual FVII activity in four patients with a single mutant allele was 23.6% (range 3-34%), which was significantly higher than that in 10 patients with two mutant alleles that was 4.6% (range 1-19%) (P=0.023). In summary, the data from this study on the largest number of FVII deficiency in Korea showed recurrent mutations in this population and suggested genotype-phenotype correlations. Blood Coagul Fibrinolysis 22:102-105 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.