Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal dysplasia in a Chinese family.
Mutation p.Leu354Pro in EDA causes severe hypohidrotic ectodermal dysplasia in a Chinese family.
复制标题
DOI：
10.1016/j.gene.2011.10.009
复制
发表时间：
2012-01
期刊：
影响因子：
3.5
通讯作者：
Yuxiang. Liu;Xiaoyan Yu;Lei Wang;Chang Li;Stephen Archacki;Changzheng Huang;Jing Yu Liu;Qing Wang;Mugen Liu;Zhao-hui Tang
中科院分区：
文献类型：
--
作者：
Yuxiang. Liu;Xiaoyan Yu;Lei Wang;Chang Li;Stephen Archacki;Changzheng Huang;Jing Yu Liu;Qing Wang;Mugen Liu;Zhao-hui Tang
X连锁隐性少汗性外胚叶发育不良（XLHED）的特征是牙齿、头发和外分泌汗腺的形态发生缺陷。它与EDA基因突变有关。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，我们确定了一个中国家庭与XLHED。EDA全编码区的直接DNA测序揭示了一个新的错义突变，p.Leu354Pro在XLHED患者的影响。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。Pro取代Leu354位于EDA的TNF样结构域，可能通过改变EDA的拓扑结构来影响正常外胚层发育所需的上皮信号通路。我们的发现拓宽了EDA突变的范围，可能有助于理解XLHED的分子基础和遗传咨询。
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.