毛囊角化病一家系及三例散发患者ATP2A2基因突变研究

Study on ATP2A2 gene mutation in a family and three sporadic patients with Darier’s disease

目的:对毛囊角化病(Darier's disease, DD)一家系及三例散发患者进行ATP2A2基因的突变分析。方法:收集先证者及其家系成员、散发病例的临床资料和外周血,采用PCR技术扩增ATP2A2基因所有编码区及侧翼序列,用Sanger法测序检测潜在的突变,选取与患者无亲缘关系的100例健康人作为对照,同时对已报道的ATP2A2基因突变进行文献回顾。结果:家系中三例患者均检测出ATP2A2基因第5号外显子c.380 G>A(p.G127D)新发错义突变;散发患者S1检测出第13号外显子C.1676G>A(p.R559Q)错义突变,散发患者S2检测出第14号外显子c. 2001C>T(p.D667D)同义突变,散发患者S3未检测出突变。结论:本研究中共发现三个突变,其中c.380G>A(p.G127D)在中国人群中首次报道,拓展了ATP2A2的基因突变谱。

Objective:To detect mutations of ATP2A2 gene in three sporadic patients and one family with Darier's Disease (DD). Methods:Clinical data and peripheral blood samples were collected from the family members, sporadic patients and 100 unrelated healthy people. PCR was performed to amplify all coding exons and flanking sequence of the ATP2A2 gene. PCR products were directly sequenced to detect mutations. Literatures were reviewed on ATP2A2 gene mutations in DD. Results:A novel missense mutation c. 380 G>A ( p.G127D ) in exon 5 of ATP2A2 gene was detected in all three patients in the family. The missense mutation C.1676G>A (p.R559Q) in exon 13 was detected in sporadic patient S1, and a synonymous mutation c. 2001C>T (p.D667D) in exon 14 was detected in sporadic patient S2. No mutation was found in the sporadic patient S3. Conclusion:Three mutations were found and c.380 G>A (p.G127D) is a newly discovered mutation in ATP2A2 gene of DH in Chinese population, which expands the mutation spectrum of ATP2A2 gene.