中国麻风皮肤病杂志 ›› 2021, Vol. 37 ›› Issue (5): 276-280.doi: 10.12144/zgmfskin202105276

• 论著 • 上一篇    下一篇

毛囊角化病九例ATP2A2基因突变研究

于学萍1,赵晴2,夏倩倩2,孙乐乐2,糜自豪2,王真真2,庞政2,于功奇2,付希安2,刘红2,张福仁1,2
  

  1. 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
  • 出版日期:2021-05-15 发布日期:2021-04-29
  • 通讯作者: 张福仁，E-mail: zhangfuren@hotmail.com

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

YU Xueping1, ZHAO Qing2, XIA Qianqian2, SUN Lele2, MI Zihao2, WANG Zhenzhen2, PANG Zheng2, YU Gongqi2, FU Xi'an2, LIU Hong2, ZHANG Furen1,2   

  1. 1 Binzhou Medical University, Yantai 264033, China; 2 Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University, Jinan 250022, China
  • Online:2021-05-15 Published:2021-04-29
  • Contact: ZHANG Furen, E-mail: zhangfuren@hotmail.com

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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。

关键词: 毛囊角化病, ATP2A2, 钙信号通路

Abstract: 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.

Key words: Darier's disease, ATP2A2, calcium signal pathway