[由Thr359Met纯合性导致的遗传性FVII缺乏家系分析]
[Analysis of an inherited FVII deficiency pedigree caused by homozygosity of Thr359Met].
作者信息
Chu Hai-yan, Wang Hong-li, Ding Qiu-lan, Wang Xue-feng, Qu Bin, Wu Fang, Kang Wen-ying, Duan Bao-hua, Yin Jun, Fu Qi-hua, Wu Wen-man, Wang Zhen-yi
机构信息
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2003 Mar;24(3):134-7.
OBJECTIVE
To explore the gene mutation type of an inherited coagulation factor VII deficiency pedigree.
METHODS
FVII:Ag, FVII:C, FVIIa were detected to classify deficiency type. FVII gene mutations were analysed in the proband and her family members by DNA directly sequencing. Biostructural pathology of the identified mutation was analysed by molecular modeling.
RESULTS
Homozygosity of C-->T transition at position 11514 in exon 8 resulting in Thr359Met was identified in the proband, and heterozygosity for Thr359Met was confirmed in her parents, her son and some other family members. Thr359Met induces CRM-deficiency. It is found by computer simulated molecular model that the replacement of Thr by Met which has a larger and longer side chain might cause steric hindrance, and change the number of H-bonds.
CONCLUSIONS
Homozygous missense mutation Thr359Met was found in a pedigree of hereditary FVII deficiency. This mutation might change the configuration of protein molecule and result in severe FVII deficiency.
目的
探讨一个遗传性凝血因子Ⅶ缺乏家系的基因突变类型。
方法
检测FVII:Ag、FVII:C、FVIIa以分类缺乏类型。通过DNA直接测序分析先证者及其家庭成员的FVII基因突变。通过分子建模分析已鉴定突变的生物结构病理学。
结果
先证者中鉴定出第8外显子11514位C→T转换的纯合性，导致Thr359Met，其父母、儿子和其他一些家庭成员中证实存在Thr359Met杂合性。Thr359Met导致CRM缺乏。通过计算机模拟分子模型发现，具有更大更长侧链的Met取代Thr可能会导致空间位阻，并改变氢键数量。
结论
在一个遗传性FVII缺乏家系中发现纯合错义突变Thr359Met。该突变可能改变蛋白质分子的构象并导致严重的FVII缺乏。
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