[两个遗传性F VII缺乏症家系的分子分析]

[Molecular analysis of two pedigrees with hereditary F VII deficiency].

作者信息

Chu Haiyan, Wang Hongli, Wang Xuefeng, Guo Xuemei, Qu Bin, Duan Baohua, Yin Jun, Kang Wenying, Wang Zhenyi

机构信息

Shanghai Institute of Haematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2002 Mar;23(3):130-3.

PMID:12015065

Abstract

OBJECTIVE

To identify the mutation of coagulation factor VII (F VII) gene in two pedigrees with hereditary F VII deficiency.

METHODS

F VII gene mutations were analysed in two propositi and their family members by direct DNA sequencing. Allele specific PCR and PCR combined with restricted enzyme digestion were used to confirm the detected mutations.

RESULTS

Two gene mutations were detected in the propositus of pedigree A: G to C transition at position 6390 resulting in Trp40Cys and G to A at 11496 resulting in Arg353Gln, both are heterozygotes. The heterozygosity for polymorphism Arg353Gln was confirmed with the restriction enzyme Msp I digestion in his mother. In the propositus of pedigree B, there was a T to G transition at position 11482 resulting in His348Gln, heterozygosity of which was confirmed with Nsp I digestion in the propositus and his daughter. G to T transition at position 11514 resulting in Thr359Met was also found in the propositus of pedigree B, and the heterozygosity for Thr359Met was confirmed with allele specific PCR in the propositus and his son.

CONCLUSION

Three missense mutations were found in two pedigrees with hereditary F VII deficiency. A novel Trp40Cys mutation was reported for the first time.

摘要

目的

鉴定两个遗传性凝血因子VII（F VII）缺乏家系中凝血因子VII基因的突变情况。

方法

采用直接DNA测序法对两个先证者及其家庭成员的F VII基因突变进行分析。采用等位基因特异性PCR和PCR结合限制性酶切法对检测到的突变进行确认。

结果

在A家系先证者中检测到两个基因突变：6390位的G突变为C，导致Trp40Cys；11496位的G突变为A，导致Arg353Gln，均为杂合子。其母亲经限制性酶Msp I酶切确认了Arg353Gln多态性的杂合性。在B家系先证者中，11482位发生T到G的转换，导致His348Gln，先证者及其女儿经Nsp I酶切确认了其杂合性。在B家系先证者中还发现11514位的G到T转换，导致Thr359Met，先证者及其儿子经等位基因特异性PCR确认了Thr359Met的杂合性。