Phenotype and genotype analysis for a consanguineous pedigree with combined coagulation factor VII and X deficiency / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To identify potential mutations and explore the molecular mechanism underlying combined inherited coagulation factors VII(FVII) and X(FX) deficiency for a family featuring consanguineous marriage between maternal cousins.</p><p><b>METHODS</b>Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII activity (FVIIC), FX activity (FXC), FVII antigen (FVIIAg), FX antigen (FXAg) and other coagulant parameters of the proband and 5 family members were measured. Potential mutations in exons, exon-intron boundaries and 5', 3' untranslated sequences of F7 and F10 genes were screened by polymerase chain reaction and direct sequencing. Suspected mutations were confirmed by sequencing the opposite strand.</p><p><b>RESULTS</b>PT and APTT of the proband were obviously prolonged to become 76.4 s and 60.2 s, respectively. FVIIC, FVIIAg,FXC and FXAg of the proband were obviously reduced to become 4%, 6%, 6% and 33%, respectively. Both PT and APTT of her grandmother, father, mother and daughter were slightly prolonged, which have measured 16.4 s, 15.8 s,16.9 s, 16.5 s, and 44.0 s, 42.1 s, 41.1 s, 43.5 s, respectively. And their FVIIC (34%, 39%, 31%, 40%, respectively), FXC (50%, 58%, 47%, 42%, respectively) and FXAg (51%, 54%, 58%, 47%, respectively) were slightly reduced, while FVIIAg was in the normal range. The coagulant parameters of her younger brother were within normal range. Two homozygous mutations, g.11267C to T in exon 8 of F7 gene, which resulted in an Arg277Cys substitution, and g.28139G to T in exon 8 of F10 gene which led to a Val384Phe substitution, were identified in the proband. The proband's grandmother, parents and daughter were heterozygous for both Arg277Cys and Val384Phe mutationss. Wild-type alleles of both F7 and F10 genes were also found in the younger brother.</p><p><b>CONCLUSION</b>A homozygous Arg277Cys mutation and a Val384Phe mutation have been respectively identified in the F7 and F10 genes, which can explain the low levels of FVII and FX in this family. The former has been inherited from the consanguineous parents.</p>