血友病A患者26例基因突变类型及其与临床表型的关系  

Gene mutation type in hemophilia A children and its relationship with clinical phenotype:a study on 26 cases

作　　者：赵雪莲[1] 王旭 付强[1] 王西阁[1] 袁二凤 夏磊[1] 李帅全 宋丽丽[1] 周玉洁[1] 臧文涛 姚小静 郝腾 樊淑丹 崔余霞 Zhao Xuelian;Wang Xu;Fu Qiang;Wang Xige;Yuan Erfeng;Xia Lei;Li Shuaiquan;Song Lili;Zhou Yujie;Zang Wentao;Yao Xiaojing;Hao Teng;Fan Shudan;Cui Yuxia(Department of Pediatric Hematology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第三附属医院小儿血液科,郑州450052

出　　处：《中国实用医刊》2024年第7期1-5,共5页Chinese Journal of Practical Medicine

基　　金：河南省医学科技攻关计划(联合共建)项目(LHGJ20190345)。

摘　　要：目的分析26例血友病A患者基因突变情况,探究基因突变与临床表型之间的关系。方法抽取2019年1月至2023年11月于郑州大学第三附属医院小儿血液科就诊并完善基因检测的血友病A患者26例进行回顾性分析,使用倒位位移聚合酶链式反应方法检测F8基因内含子22、内含子1的倒位,多重连接依赖式探针扩增法检测F8基因大片段缺失/重复,高通量测序技术检测F8基因点突变;采用一期法检测凝血因子Ⅷ活性水平(FⅧ:C),并根据患者FⅧ:C将其分为:轻型血友病A、中型血友病A、重型血友病A。结果26例血友病A患者中轻型6例,中型8例,重型12例。26例血友病A患者中内含子22倒位有4例(15.4%),内含子1倒位有1例(3.8%),错义突变有8例(30.7%),无义突变有1例(3.8%),移码突变6例(23.1%),大片段缺失有3例(11.8%),剪切位点突变有2例(7.6%),未检测到突变有1例(3.8%)。26例血友病A患者的基因检测结果中,共发现5种新发现的基因突变。25例检测出基因突变患者中有22例完善家系验证,其中19例患者的母亲为携带者,3例患者为自发突变。结论本研究中发生率最高的基因突变类型为错义突变,在重型血友病A中最常见的基因突变为移码突变和内含子倒位,在中型血友病A最常见的基因突变为错义突变,在轻型血友病A最常见的基因突变为错义突变。完善基因检测可明确诊断,避免误诊,更好地进行遗传咨询,同时可检测到新发现的突变以补充F8基因数据库。Objective To analyze the gene mutation in 26 patients with hemophilia A,and to investigate the relationship between gene mutations and clinical phenotypes.Methods A total of 26 patients with hemophilia A who saw doctors in Department of Pediatric Hematology of the Third Affiliated Hospital of Zhengzhou University and underwent genetic testings from January 2019 to November 2023 were selected for the retrospective analysis.The inversion of intron 22 and intron 1 of F8 gene were detected using inverse shifting-polymerase chain reaction.Multiplex ligation-dependent probe amplification was used to detect large deletions/duplication in the F8 gene.Next-generation sequencing was used to detect point mutations in the F8 gene.The level of factorⅧcoagulation activity(FⅧ:C)was measured using a one-stage test,by which the patients were classified(mild hemophilia A,medium hemophilia A and severe hemophilia A).Results Among the 26 patients with hemophilia A,there were 6 patients with mild hemophilia A,8 patients with medium hemophilia A,and 12 patients with severe hemophilia A.Among the 26 patients with hemophilia A,there were 4 cases(15.4%)intron 22 inversion,1 case(3.8%)intron 1 inversion,8 cases(30.7%)missense mutation,1 case(3.8%)nonsense mutation,6 cases(23.1%)frameshift mutation,3 cases(11.8%)large deletion,2 cases(7.6%)splicing defects,and 1 case(3.8%)no mutation detected.A total of 5 newly identified mutations were found by the genetic test among the 26 patients with hemophilia A.Among the 25 patients with gene mutations,22 cases undergone complete family verification.Among them,19 patients had carrier mothers,and 3 patients had spontaneous mutations.Conclusions The type of mutation with the highest incidence in the study is missense mutation,the top two most common mutation type in severe hemophilia A are intron inversion and frameshift mutation;the most common mutation in medium hemophilia A is missense mutation;and the most common mutation in mild hemophilia A is missense mutation.Improved genetic testing is co

关 键 词：血友病A 基因突变 凝血因子 

分 类 号：R554.1[医药卫生—血液循环系统疾病]