Genotypic and phenotypic analysis of a case with inherited coagulation factor X deficiency

Objective To explore the correlation between F10 gene mutation and its phenotype in a Chinese pedigree affected with FⅩ deficiency. Methods Prothrombin time(PT), activated partial thromboplastin time(APTT), fibrinogen, FⅡ activity(FⅡ∶C), FⅦ activity(FⅦ∶C), FⅨ activity(FⅨ∶C), FⅩ activity(FⅩ∶C) were determined with a one-stage clotting assay. The FⅩ antigen(FⅩ∶Ag) was detected with an enzyme linked immunosorbent assay(ELISA). The 8 exons, introns and 5′ and 3′ untranslated regions(UTR) of the F10 gene of the proband and her family members were subjected to PCR amplification and Sanger sequencing. Suspected mutation was confirmed by reverse sequencing. Polymorphisms were excluded by direct sequencing of 100 healthy individuals. Results The PT and APTT of the proband have prolonged to 16.1 s and 49.0 s, respectively. Her FⅩ∶C and FⅩ∶Ag were reduced by 27% and 56%, and her mother’s PT, APTT, FⅩ∶C and FⅩ: Ag were 14.8 s, 37.4 s, 44%, 34%, respectively. Her grandmother’s PT, APTT, FⅩ∶C and FⅩ∶Ag were 15.8 s, 42.2 s, 31%, 45%, respectively. The results of her father and other family members were all within the normal range. Genetic analysis has revealed a heterozygous G>A mutation in the proband at position 28076 in exon 8 of the F10 gene, which resulted in a p. Gly363Ser substitution. The same mutation was also found in her mother and grandmother. No mutation of the F10 gene was found in her father. Gly363Ser may result in changes in the secondary structure of the FⅩ protein and reduction of its activity. Conclusion The g. 28076G>A(p.Gly363Ser) mutation of the F10 gene probably underlies the FⅩ deficiency in this pedigree. The mutation was discovered for the first time in Chinese patients. Key words: Coagulation factor Ⅹ deficiency; Gene mutation; Coagulation activity