毛囊角化病九例ATP2A2基因突变研究  

Mutation detection of ATP2A2 gene in 9 patients with Darier s disease

作　　者：于学萍 赵晴 夏倩倩 孙乐乐[2] 糜自豪 王真真[2] 庞政 于功奇[2] 付希安[2] 刘红[2] 张福仁 YU Xueping;ZHAO Qing;XIA Qianqian;SUN Lele;MI Zihao;WANG Zhenzhen;PANG Zheng;YU Gongqi;FU Xi an;LIU Hong;ZHANG Furen(Binzhou Medical University,Yantai 264033,China;Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and Venereology,Shandong First Medical University,Jinan 250022,China)

机构地区：[1]滨州医学院,山东烟台264033 [2]山东第一医科大学附属皮肤病医院(山东省皮肤病医院,山东省皮肤病性病防治研究所),济南250022

出　　处：《中国麻风皮肤病杂志》2021年第5期276-280,共5页China Journal of Leprosy and Skin Diseases

基　　金：山东省高等学校青创科技支持计划(编号:2019KJL003);山东省医学科学院创新工程。

摘　　要：目的:检测9例毛囊角化病(Darier s disease,DD)患者的基因突变。方法:提取1家系中2例患者、7例散发患者及100名正常对照外周血基因组DNA,用Sanger测序检测9例DD患者ATP2A2的致病突变。对不携带ATP2A2突变的患者,应用全外显子组测序(WES)寻找可能导致该疾病的其他变异。364名健康对照被纳入突变筛选。可疑的变异通过Sanger测序进行确认。结果:通过Sanger测序,我们发现9例DD患者中有5例出现了ATP2A2突变,包括1例报道过的突变和3例新突变。在其余病例中,WES鉴定了四个ATP酶基因(ITPR3、ATP2B2、RYR1和PLCB1)中的4个变异,均参与钙信号通路。结论:本研究中发现了4个ATP2A2基因突变,其中3个为新发突变,丰富了ATP2A2基因突变谱,并提示四种ATP酶基因变异可能与DD相关。Objective:To detect the genetic mutations in 9 cases with Darier s disease(DD)by Sanger sequencing and whole exome sequencing(WES).Methods:The genomic DNA was extracted from peripheral blood of 2 patients from one family,7 sporadic patients and 100 normal controls.Sanger sequencing was used to detect ATP2A2 pathogenic mutations in 9 DD patients.In the patients with non-mutations of ATP2A2,the whole exome sequencing(WES)was performed to search for other variants that may potentially cause this disease.Three hundred and sixty-four healthy controls were included for mutation screening.Suspected variants were confirmed by Sanger sequencing.Results:By Sanger sequencing,we found that 5 patients had ATP2A2 mutation,including 1 reported mutation and 3 new mutations.In other cases,four variants in four ATPase genes(ITPR3,ATP2B2,RYR1,and PLCB1)were identified by WES,all of which were involved in calcium signal pathway.Conclusion:In this study,four mutations in ATP2A2 gene were identified including 3 novel mutations,which broaden the spectrum of ATP2A2 mutations.Moreover,our study suggests that four ATPase gene variants may be associated with DD.

关 键 词：毛囊角化病 ATP2A2 钙信号通路 

分 类 号：R751[医药卫生—皮肤病学与性病学]