F9基因多碱基缺失突变导致乙型血友病家系遗传学分析  

Genetic analysis for a haemophilia B family with multi nucleotides deletion mutation of F9 gene

作　　者：李涛 吕雪 肖海 郭谦楠 王红丹 张波 张朝阳 王鑫 许泼实 廖世秀 Li Tao;Lyu Xue;Xiao Hal;Guo Qianaan;Wang Hongdan;Zhang Bo;Zhang Chaoyang;Wang Xin;Xu Poshi;Liao Shixiu(Department of Laboratory Medicine,Henan Province People＇s Hospital,Central China Fuwai Hospital,Zhengzhou 451478,China)

机构地区：[1]河南省人民医院、阜外华中心血管病医院、河南省人民医院心脏中心、郑州大学人民医院医学检验科,郑州451478 [2]河南省人民医院、郑州大学人民医院健康管理科 [3]河南省人民医院、郑州大学人民医院医学遗传研究所

出　　处：《中华检验医学杂志》2018年第9期675-679,共5页Chinese Journal of Laboratory Medicine

基　　金：河南省科技攻关计划项目（162102310294）;河南省医学科技攻关计划项目（201602249）

摘　　要：目的 对1个F9基因多碱基缺失突变家系进行基因诊断及产前诊断.方法 遗传学分析.利用PCR-测序技术检测2013年4月到河南省人民医院咨询乙型血友病家系7例患者F9基因全外显子突变情况,根据患者F9基因突变情况对家系中非乙型血友病患者和100名健康人进行基因检测以排除多态性.根据上述乙型血友病基因检测结果来明确家系中F9基因致病性突变,并指导家系中女性携带者进行产前诊断,建议乙型血友病女性携带者孕中期抽取羊水进行胎儿基因检查,同时根据基因检测结果告知其所怀胎儿为非乙型血友病胎儿.结果 PCR-测序结果显示7例患者F9基因均存在c.185_188delGAGA[p.Glu62Asnfs？41]突变,使F9基因阅读框发生移码突变,在突变位点后第41位密码子存在TAA终止密码,导致F9基因翻译提前终止.家系中非乙型血友病男性和100名健康人此区域未见突变.该家系受检者中共检测出8名携带者女性,9名非携带者女性,对其中1名携带者女性进行产前诊断,羊水标本性别决定基因（SRY）阳性,F9基因c.185_188未见缺失突变.结论 明确了该家系的F9基因致病性突变,并指导了携带者女性进行产前诊断.Objective To conduct genetic diagnosis and prenatal diagnosis for a haemophilia B family with multi-nucleotides deletion mutation of F9 gene.Methods This is a genetic analysis.Whole exon mutation of the F9 gene was analyzed by PCR and Sanger sequencing for seven patients with the family of hemophilia B who consulted doctors in Henan Province People′s Hospital in April 2013.Suspected mutation was verified among non-hemophilia B members of the family and 100 healthy controls to rule out genetic polymorphism of the F9 gene.The above-mentioned detection results of hemophilia B gene , the pathogenic mutation of F9 gene in the family was clarified , and prenatal diagnosis was conducted for the female carriers in the family.It is recommended that the fetal gene detection should be conducted in amniotic fluid in the mid-term pregnancy of the female carriers of hemophilia , and then they can be informed of the non-hemophilia B fetus by the results of the gene detection .Results PCR and sequencing analysis has identified a deletion mutation of F9 gene c.185_188delGAGA[p.Glu62Asnfs？41]in seven hemophilia B patients.This mutation induced F9 gene frame shift mutation which led to early termination of F9 gene translation because there was a termination codon TAA at the 41th codon after the mutation site.The same mutation was not found among the non-hemophilia B members of the family and the 100 healthy controls. There were eight female carriers and nine female non-carriers in the family.Upon prenatal diagnosis , the Y chromosome sex-determining gene （ SRY ） in amniotic fluid was positive and no deletion mutation was observed in the F9 gene c.185_188.Conclusion The pathogenic mutation of F9 gene in the family was identified , which was helpful for prenatal diagnosis in female carriers .

关 键 词：血友病B 基因缺失 产前诊断 基因检测 

分 类 号：R554.1[医药卫生—血液循环系统疾病] R440[医药卫生—内科学]