[Gene analysis of a combined inherited factor VII and factor X deficiency pedigree].

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Ming-shan Wang, Yan-hui Jin, Fang-xiu Zheng, Hai-xiao Xie, Peng-fei Xu, Zhen-zhen Niu
• Journal: Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi (Zhonghua Xue Ye Xue Za Zhi) Vol. 32 Issue 12 Pg. 854-7 (Dec 2011) ISSN: 0253-2727 [Print] China
• PMID: 22339961 (Publication Type: English Abstract, Journal Article)

Chemical References

• Factor VII

Topics

• Adolescent
• Adult
• Base Sequence
• DNA Mutational Analysis
• Factor VII (genetics)
• Factor VII Deficiency (complications, genetics)
• Factor X Deficiency (complications, genetics)
• Female
• Heterozygote
• Humans
• Male
• Middle Aged
• Mutation
• Pedigree
• Young Adult