山东省55例血友病A患者基因检测及分析  

Gene detection and analysis of 55 patients with hemophilia A in Shandong Province

作　　者：张文慧 陈昀[1] 常亚丽[1] 周亚伟[1] 房云海[2] 张心声[2] 郭农建[1] ZHANG Wenhui;CHEN Yun;CHANG Yali;ZHOU Yawei;FANG Yunhai;ZHANG Xinsheng;GUO Nongjian(Department of Hematology,Jinan Central Hospital Affiliated to Shandong University,Jinan 250013,Shandong,China;Hemophilia Treatment Center of Shandong Province,Blood Center of Shandong Province,Jinan 250013,Shandong,China)

机构地区：[1]山东大学附属济南市中心医院血液科,山东济南250013 [2]山东省血液中心山东省血友病诊疗中心,山东济南250013

出　　处：《山东大学学报（医学版）》2019年第12期57-61,共5页Journal of Shandong University:Health Sciences

摘　　要：目的分析山东省55例血友病A(HA)患者基因突变类型,探讨HA发病机制。方法采用LD-PCR法检测山东省55例HA患者凝血因子Ⅷ(FⅧ)基因的内含子22倒位突变,阴性者采用高通量测序法检测FⅧ基因的26个外显子,并与人类基因突变数据库比对。结果55例HA患者中内含子22倒位突变20例,其他35例共检测到28种突变类型,其中3例同时检测出2种突变,有6例未检测到基因突变。共发现c.20342062del、c.60526058del、c.60466047del、c.1009+1G>T、c.2997dupA、c.4001delT、c.1334T>A、c.1493G>A、c.557A>T等9种未被报道过的新突变。结论FⅧ基因突变是导致HA的根本原因。重型血友病患者中最常见的突变类型为内含子22倒位突变。编码区突变最常见的突变类型为错义突变。新发现的9种新突变丰富了基因突变谱,为探讨HA发病机制提供了基础。Objective To analyze the genetic mutation types of 55 patients with hemophilia A(HA)in Shandong Province,and explore its molecular mechanism.Methods The intron 22 inversion mutation of factorⅧ(FⅧ)in all patients was detected with LD-PCR.The 26 exons of FⅧnegative patients were detected with next-generation sequencing and matched in the humangene mutation database.Results Of all 55 patients,20 had intron 22 inversion mutation,and the other 35 had 28 different types of mutations,of whom 3 had 2 simultaneous mutations,while 6 had no mutation.Altogether 9 new mutation types unreported before were discovered,including c.20342062 del,c.60526058 del,c.60466047 del,c.1009+1 G>T,c.2997 dupA,c.4001 delT,c.1334 T>A,c.1493 G>A and c.557 A>T.Conclusion FⅧmutation is the direct cause of HA.The most common mutation in severe HA is intron 22 inversion mutation.The most common mutation in coding region mutation is the missense.The 9 new mutations discovered in the study enrich the gene mutation profile and provide reference for the study of HA pathogenesis.

关 键 词：血友病A 凝血因子Ⅷ 基因突变 内含子22倒位 基因测序 

分 类 号：R574[医药卫生—消化系统]