Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, PR China.
Gene. 2012 Jan 10;491(2):246-50. doi: 10.1016/j.gene.2011.10.009. Epub 2011 Oct 10.
X-linked recessive hypohidrotic ectodermal dysplasia (XLHED) is characterized by the defective morphogenesis of teeth, hair, and eccrine sweat glands. It is associated with mutations in the EDA gene. Up to now, more than 100 mutations in the EDA gene have been reported to cause XLHED. The product of EDA gene is a trimeric type II transmembrane protein that belongs to the tumor necrosis factor (TNF) family of ligands. In this study, we identified a Chinese family with XLHED. Direct DNA sequencing of the whole coding region of EDA revealed a novel missense mutation, p.Leu354Pro in a patient affected with XLHED. This mutation was not found in either unaffected male individuals of the family or 168 normal controls. The substitution of Leu354 with Pro was found to be located in the TNF-like domain of EDA and may influence the epithelial signaling pathway required for the normal ectodermal development through altering the topology of EDA. Our finding broadens the spectrum of EDA mutations and may help to understand the molecular basis of XLHED and aid genetic counseling.
X 连锁隐性汗孔发育不良（XLHED）的特征是牙齿、毛发和外分泌汗腺的形态发生缺陷。它与 EDA 基因的突变有关。到目前为止，已经报道了超过 100 种 EDA 基因突变导致 XLHED。EDA 基因的产物是一种三聚体 II 型跨膜蛋白，属于肿瘤坏死因子（TNF）配体家族。在这项研究中，我们鉴定了一个患有 XLHED 的中国家族。对 EDA 的整个编码区进行直接 DNA 测序，发现了一个新的错义突变，p.Leu354Pro，在一个受 XLHED 影响的患者中。该突变在家族中未受影响的男性个体或 168 名正常对照中均未发现。EDA 的 TNF 样结构域中 Leu354 被 Pro 取代，可能通过改变 EDA 的拓扑结构，影响上皮信号通路，从而影响正常的外胚层发育。我们的发现拓宽了 EDA 突变谱，有助于理解 XLHED 的分子基础，并有助于遗传咨询。
