Arg304Trp导致的遗传性凝血因子Ⅶ缺陷症家系分析  

Analysis of an inherited coagulation factor Ⅶ deficiency pedigree caused by Arg304Trp

作　　者：郑芳秀[1] 王明山[1] 金艳慧[1] 谢海啸[1] 谢耀盛[1] 牛真珍[1] 徐鹏飞[1] 

机构地区：[1]温州医学院附属第一医院实验诊断中心,温州325000

出　　处：《中国优生与遗传杂志》2011年第4期22-23,34,共3页Chinese Journal of Birth Health & Heredity

摘　　要：目的对1例姨表近亲结婚的遗传性凝血因子Ⅶ(coagulation factorⅦ,FⅦ)缺陷症家系进行表型与基因型分析。方法检测血浆中凝血酶原时间(prothrombin time,PT)、FⅦ促凝活性(FⅦprocoagulant activity,FⅦ:C)及其它凝血指标以明确诊断;用DNA直接测序法对先证者及家庭成员FⅦ基因的全部外显子及其侧翼、启动子区进行分析,寻找基因突变,用反向测序证实所发现的突变。结果先证者的PT和FⅦ:C明显异常,分别为35.1s和3%;其父亲、母亲、大儿子和小儿子的PT稍延长,FⅦ:C明显降低。先证者FⅦ基因外显子8存在11348C→T纯合突变导致Arg304Trp;其父亲为该突变位点的杂合子,其母亲、大儿子和小儿子均为Arg304Trp杂合突变和Arg353Gln杂合多态性。结论先证者纯合突变Arg304Trp遗传自近亲结婚且具有相同杂合突变位点的父母。Arg353Gln多态性可能不是影响该家系成员血浆FⅦ:C水平的主要因素。Objective： To analyze the phenotype and genotype of an inherited coagulation factor Ⅶ deficiency pedigree with a relationship between maternal cousin consanguineous marriage.Methods： The diagnosis was validated by coagulant parameter assay on prothrombin time（PT）,FⅦ procoagulant activity（FⅦ：C） and so on.FⅦ gene mutations were analysed in the proband and other family members by DNA direct sequencing of PCR products of all exons,exon-intron boundaries and promoter.The mutations were confirmed by reverse sequencing.Results： The value of PT and FⅦ activity of the proband showed significantly abnormal,which was 35.1s and 3% respectively.The PT of his father,mother,eldest son and youngest son was prolonged slightly and the FⅦ activity was reduced obviously.Homozygous mutation of C→T transition at position 11348 in exon 8 resulting in Arg304Trp was identified in the proband,and his father was heterozygous for Arg304Trp.His mother,eldest son and youngest son were all heterozygous for Arg304Trp and Arg353Gln polymorphism.Conclusion： The homozygous mutation Arg304Trp resulted from heterozygous mutation of his parents with consanguineous marriage.Arg353Gln polymorphism may not be the main reason that affected the level of FⅦ activity in other family members.

关 键 词：遗传性凝血因子Ⅶ缺陷症 临床表型 基因突变 多态性 

分 类 号：R554[医药卫生—血液循环系统疾病]