Peking University School and Hospital of Stomatology, Department of Pediatric Dentistry, & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China; Peking University International Hospital, Department of Stomatology, 1# Life Science Park Road, Changping District, Beijing, China.
Peking University School and Hospital of Stomatology, Department of Pediatric Dentistry, & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR China.
Arch Oral Biol. 2019 Nov;107:104507. doi: 10.1016/j.archoralbio.2019.104507. Epub 2019 Jul 24.
X-linked hypohidrotic ectodermal dysplasia (XLHED) can be characterized by hypohidrosis, sparse hair, hypodontia, and characteristic facial features and is usually caused by mutations of ectodysplasin A (EDA) gene located on the X chromosome. In this study, we examined a HED pedigree and studied the molecular genetics of the disease. A novel missense mutation was revealed by direct sequencing analysis in the EDA exon 7 (c.913 A > C, p.S305R). The impact of the mutation on the protein was studied in vitro in human embryonic kidney 293 T cells transfected with mutant or wild type forms of EDA. The mutant-type EDA1 protein showed impaired solubility comparing with wild-type EDA1. This novel missense EDA mutation was considered to be the cause of HED in the pedigree reported here. Our findings, combined with those reported elsewhere, provide an improved understanding of the pathogenic mechanism of HED as well as important information for a genetic diagnosis.
X 连锁性汗孔发育不良（XLHED）的特征为少汗、毛发稀疏、牙齿缺失以及具有特征性的面部特征，通常由位于 X 染色体上的外胚层发育不良蛋白 A（EDA）基因突变引起。在本研究中，我们检测了一个 HED 家系，并研究了该疾病的分子遗传学。通过直接测序分析在 EDA 外显子 7 中发现了一个新的错义突变（c.913 A > C，p.S305R）。在转染突变型或野生型 EDA 的人胚肾 293T 细胞中体外研究了该突变对蛋白的影响。与野生型 EDA1 相比，突变型 EDA1 蛋白的可溶性降低。该新型 EDA 错义突变被认为是本报告家系中 HED 的致病原因。我们的发现与其他报道相结合，为 HED 的发病机制提供了更深入的理解，也为遗传诊断提供了重要信息。
