Shandong Provincial Hospital for Skin Diseases & Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
J Dermatol. 2021 Jul;48(7):989-992. doi: 10.1111/1346-8138.15828. Epub 2021 Apr 20.
Hailey-Hailey disease (HHD) is an autosomal dominant monogenic disease that is defective in the ATP2C1 gene. In previous studies, Sanger sequencing was the main method applied to detect mutations in HHD patients, and no mutations in the ATP2C1 gene were found in 12-55% of those reported. The aim of our study was to carry out whole exome sequencing (WES) for the HHD patients in whom efforts to identify mutations by Sanger sequencing had failed, and to find a new pathogenic gene. WES was performed using genomic DNA from 13 HHD patients and 364 in-house healthy controls. Potential pathogenic mutations were subsequently validated by Sanger sequencing. As a result, eight mutations in the ATP2C1 gene were identified using WES. In the remaining five patients, we found one mutation in the ATP2A2 gene which was the causal gene of Darier's disease. Four patients had no detectable mutations in ATP2C1 and the other ATPase genes. Together with our previous study in 2019, the total mutation rate was calculated to be 47/52 (90.4%). These findings demonstrate that WES is capable of improving the mutation detection sensitivity in HHD compared with Sanger sequencing.
Hailey-Hailey 病（HHD）是一种常染色体显性单基因遗传病，缺陷基因位于 ATP2C1 基因。在以前的研究中，桑格测序是用于检测 HHD 患者突变的主要方法，但在报道的病例中，有 12%-55%的患者未发现 ATP2C1 基因的突变。本研究的目的是对桑格测序未能识别突变的 HHD 患者进行全外显子组测序（WES），以寻找新的致病基因。使用 13 例 HHD 患者和 364 例内部健康对照的基因组 DNA 进行 WES。随后通过 Sanger 测序验证潜在的致病突变。结果，通过 WES 鉴定出 ATP2C1 基因中的 8 个突变。在其余 5 名患者中，我们发现了 ATP2A2 基因中的一个突变，该突变为 Darier 病的致病基因。4 名患者在 ATP2C1 和其他 ATP 酶基因中未检测到可检测的突变。结合我们 2019 年的研究，总突变率计算为 47/52（90.4%）。这些发现表明，与桑格测序相比，WES 能够提高 HHD 中的突变检测灵敏度。
