Genotypic and phenotypic analysis of a case with inherited coagulation factor X deficiency / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the correlation between F10 gene mutation and its phenotype in a Chinese pedigree affected with FX deficiency.</p><p><b>METHODS</b>Prothrombin time(PT), activated partial thromboplastin time(APTT), fibrinogen, FII activity(FIIC), FVII activity(FVIIC), FIX activity (FIXC), FX activity(FXC) were determined with a one-stage clotting assay. The FX antigen(FXAg) 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.</p><p><b>RESULTS</b>The PT and APTT of the proband have prolonged to 16.1 s and 49.0 s, respectively. Her FXC and FXAg were reduced by 27% and 56%, and her mother's PT, APTT, FXC and FXAg were 14.8 s, 37.4 s, 44%, 34%, respectively. Her grandmother's PT, APTT, FXC and FXAg 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 to 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.</p><p><b>CONCLUSION</b>The g.28076G to 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.</p>