由双杂合突变Arg304Gln和Arg304Trp引起的遗传性凝血因子VII缺乏症

[Inherited coagulation factor VII deficiency caused by double heterozygotic mutations Arg304Gln and Arg304Trp].

作者信息

Ding Qiu-lan, Wang Hong-li, Wang Xue-feng, Wang Ming-shan, Fu Qi-hua, Wu Wen-man, Hu Yi-qun, Wang Zhen-yi

机构信息

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

出版信息

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003 Aug;20(4):279-83.

PMID:12903033

Abstract

OBJECTIVE

To investigate the genotypes of mutations of an inherited coagulation factor VII(F VII) deficiency pedigree.

METHODS

The diagnosis was validated by coagulant parameters. F VII gene mutations were analysed in the proband and her family members by DNA direct sequencing. The PCR fragments were cleaved by the Msp I restriction enzyme to confirm the mutations detected by sequencing was performed in this study.

RESULTS

Double heterozygous mutations at the same coding site of amino acid were detected in propositus of the pedigree: a C to T mutation at position 11348 resulting in Arg304Trp substitution combined with a G to A mutation at position 11349 resulting in Arg304Gln substitution. Her farther had a G to A mutation at position 11349 and her mother had a C to T mutation at position 11348, respectively. Both were heterozygous mutations. One of her brothers had normal genotype, the other brother and all her three offsprings had heterozygous mutations.

CONCLUSION

Double heterozygous mutations coding the same amino acid were found in a pedigree with hereditary coagulation factor VII deficiency.

摘要

目的

研究一个遗传性凝血因子VII（F VII）缺乏家系的基因突变类型。

方法

通过凝血参数验证诊断。采用DNA直接测序法对先证者及其家庭成员的F VII基因突变进行分析。本研究对PCR片段用Msp I限制性内切酶进行酶切，以确认测序检测到的突变。

结果

在该家系的先证者中检测到同一氨基酸编码位点的双杂合突变：11348位的C突变为T，导致Arg304Trp替换，同时11349位的G突变为A，导致Arg304Gln替换。其父亲在11349位有一个G突变为A的突变，母亲在11348位有一个C突变为T的突变，均为杂合突变。她的一个兄弟基因型正常，另一个兄弟和她的三个子女均有杂合突变。