Gene analysis of a combined inherited factor VII and factor X deficiency pedigree / 中华血液学杂志

<p><b>OBJECTIVE</b>To perform gene analysis and family survey of a patient with combined inherited FVII and FX deficiency, and to identify the gene mutation of this patient.</p><p><b>METHODS</b>The phenotype diagnosis was validated by coagulant parameter assay on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, FVII and FX activity (FVII:C, FX:C) and FVII and FX antigen (FVII:Ag, FX:Ag). FVII and FX gene mutations were analyzed in the proband and other family members by DNA direct sequencing of all exons, exon-intron boundaries and 5', 3' untranslated sequences. One hundred and six health examination participants were selected as control.</p><p><b>RESULTS</b>The values of PT and APTT of the proband showed significantly prolonged, which were 84.5s and 63.4s, respectively. The levels of FVII:C, FVII:Ag, FX:C and FX:Ag were 6%, 7%, 4% and 30%, respectively. The PT of his father, mother and sister was prolonged slightly while both APTT and FVII:Ag were in the normal range. Two homozygous mutations, g.11267C→T in exon 8 of FVII gene resulting in the substitution of Arg277Cys and g.28139G→T in exon 8 of FX gene leading to the substitution of Val384Phe, were identified in the proband. The proband's parents and sister were heterozygous for Arg277Cys and Val384Phe mutations.</p><p><b>CONCLUSION</b>Homozygous mutation Arg277Cys in FVII gene and Val384Phe in FX gene were the molecular mechanism causing combined inherited FVII and FX deficiency. The Val384Phe substitution was a novel mutation, which may affect the synthesis or secretion of FX protein.</p>

An inherited coagulation factor VII deficiency pedigree caused by homozygous mutation of His348Gln / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the gene mutation and the molecular pathogenesis of an inherited coagulation factor VII (F VII) deficiency pedigree with consanguineous marriage.</p><p><b>METHODS</b>The diagnosis was validated by coagulant parameter assay on the prothrombin time (PT), activated partial thromboplastin time, fibrinogen and coagulation factor activity. F VII gene mutations were analyzed in the proband and other family members by direct DNA sequencing of the PCR products of all exons, exon-intron boundaries and 5'and 3' untranslated sequences. The mutations were confirmed by reverse sequencing.</p><p><b>RESULTS</b>The values of PT and F VII activity in the proband were significantly abnormal, they were 30.9 s and 3% respectively. The PT of her daughter, father and mother was slightly extended to 21.2 s, 16.3 s and 16.1 s respectively, and the F VII activity was reduced to 22%, 25% and 35% respectively. The coagulant parameters of her younger brother were within normal range. Homozygous T-->G transition at position 11482 in exon 8 was identified in the proband resulting in His348Gln, and heterozygosity for His348Gln was confirmed in her daughter and her parents, and the normal wild-type was observed in her younger brother.</p><p><b>CONCLUSION</b>Homozygous missense mutation of His348Gln was found in a pedigree of hereditary F VII deficiency. The mutation was inherited from her heterozygote parents.</p>