Jin Yan-hui, Wang Ming-shan, Niu Zhen-zhen, Xie Yao-sheng, Xie Hai-xiao, Yang Li-hong
Diagnosis Center of Clinical Laboratory, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, 325000 PR China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2011 Feb;28(1):10-3. doi: 10.3760/cma.j.issn.1003-9406.2011.01.003.
To investigate the gene mutation and the molecular pathogenesis of an inherited coagulation factor VII (F VII) deficiency pedigree with consanguineous marriage.
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.
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.
Homozygous missense mutation of His348Gln was found in a pedigree of hereditary F VII deficiency. The mutation was inherited from her heterozygote parents.
研究一个近亲结婚的遗传性凝血因子VII（F VII）缺乏家系的基因突变及分子发病机制。
通过检测凝血酶原时间（PT）、活化部分凝血活酶时间、纤维蛋白原及凝血因子活性等凝血参数来验证诊断。采用对所有外显子、外显子-内含子边界以及5'和3'非翻译序列的PCR产物进行直接DNA测序的方法，对先证者及其他家庭成员的F VII基因突变进行分析。通过反向测序对突变进行确认。
先证者的PT值和F VII活性显著异常，分别为30.9秒和3%。其女儿、父亲和母亲的PT分别轻度延长至21.2秒、16.3秒和16.1秒，F VII活性分别降至22%、25%和35%。其弟弟的凝血参数在正常范围内。在先证者中鉴定出第8外显子11482位发生纯合性T→G转换，导致His348Gln，在其女儿和父母中证实为His348Gln杂合子，在其弟弟中观察到正常野生型。
在一个遗传性F VII缺乏家系中发现了His348Gln纯合错义突变。该突变由其杂合子父母遗传而来。
