Jin Yan-hui, Wang Ming-shan, Zheng Fang-xiu, Xie Yao-sheng, Xie Hai-xiao, Xu Peng-fei
Wenzhou Medical College, Wenzhou, Zhejiang, People's Republic of China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Aug;29(4):404-7. doi: 10.3760/cma.j.issn.1003-9406.2012.04.006.
To investigate potential mutations and clinical features of 9 unrelated patients with inherited coagulation factor VII (FVII) deficiency.
Clinical diagnosis was validated by assaying of coagulation parameters including prothrombin time, activated partial thromboplastin time, FVII activity and specific antigens. All exons, exon-intron boundaries, and 5' and 3' untranslated regions of F7 genes were amplified with PCR. Potential mutations were detected by direct sequencing of purified PCR products. Suspected mutations were confirmed by sequencing of the opposite strand.
All probands have featured prolonged prothrombin time, with FVII activity ranging between 2.0% to 6.0%. The titers of FVII antigen were significantly reduced in 7 probands. Eight mutations, including 6 missense mutations, 1 deletion and 1 insertion, were identified, among which 3 (Gln100Leu, Ser269Pro and g.11520_11521insT) were not described previously. Six mutations have located in the protease domain. All mutations were inherited, and consanguineous marriages were reported in 5 families. Mutations g.27_28delCT, Cys329Gly, Arg304Trp and His348Gln have been identified in unrelated families. There was a lack of correlation between the mutations and their clinical features. Two individuals with homozygous His348Gln mutations and 1 individual with homozygous Arg304Trp mutation were only mildly affected or asymptomatic. Two patients, who have respectively carried homozygous and heterozygous deletions of g.27_28delCT, were moderately affected and asymptomatic. In 4 patients carrying double heterozygous mutations, 1 (Ser269Pro and Cys329Gly) was asymptomatic, 2 (Arg304Trp and Cys329Gly, Arg277Cys and g.11520_11521insT, respectively) had a mild bleeding tendency, whilst 1 (Gln100Leu and His348Gln) has a moderate bleeding diathesis.
There seem to be hotspots of F7 gene mutations in ethnic Han Chinese populations. And there is a lack of correlation between particular types of mutations and clinical phenotypes.
研究9例无亲缘关系的遗传性凝血因子VII（FVII）缺乏症患者的潜在突变及临床特征。
通过检测凝血参数（包括凝血酶原时间、活化部分凝血活酶时间、FVII活性和特异性抗原）对临床诊断进行验证。用聚合酶链反应（PCR）扩增F7基因的所有外显子、外显子 - 内含子边界以及5'和3'非翻译区。通过对纯化的PCR产物进行直接测序检测潜在突变。通过对互补链测序确认可疑突变。
所有先证者均有凝血酶原时间延长的特征，FVII活性在2.0%至6.0%之间。7例先证者的FVII抗原滴度显著降低。共鉴定出8种突变，包括6种错义突变、1种缺失和1种插入，其中3种（Gln100Leu、Ser269Pro和g.11520_11521insT）此前未被描述。6种突变位于蛋白酶结构域。所有突变均为遗传性，5个家系报告有近亲结婚情况。g.27_28delCT、Cys329Gly、Arg304Trp和His348Gln突变在无亲缘关系的家系中被鉴定出。突变与其临床特征之间缺乏相关性。2例His348Gln纯合突变个体和1例Arg304Trp纯合突变个体仅受到轻度影响或无症状。2例分别携带g.27_28delCT纯合缺失和杂合缺失的患者，前者受到中度影响，后者无症状。在4例携带双重杂合突变的患者中，1例（Ser269Pro和Cys329Gly）无症状，2例（分别为Arg304Trp和Cys329Gly、Arg277Cys和g.11520_11521insT）有轻度出血倾向，而1例（Gln100Leu和His348Gln）有中度出血素质。
汉族人群中似乎存在F7基因突变热点。特定类型的突变与临床表型之间缺乏相关性。
