Wohlfart Sigrun, Söder Stephan, Smahi Asma, Schneider Holm
Department of Pediatrics, German Competence Center for Children with Ectodermal Dysplasias, University Hospital Erlangen, Erlangen, Germany.
Department of Pathology, University Hospital Erlangen, Erlangen, Germany.
Am J Med Genet A. 2016 Jan;170A(1):249-53. doi: 10.1002/ajmg.a.37412. Epub 2015 Oct 5.
Hypohidrotic ectodermal dysplasia (HED) is a rare disorder characterized by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth. HED forms that are caused by mutations in the genes EDA, EDAR, or EDARADD may show almost identical phenotypes, explained by a common signaling pathway. Proper interaction of the proteins encoded by these three genes is important for the activation of the NF-κB signaling pathway and subsequent transcription of the target genes. Mutations in the gene EDARADD are most rarely implicated in HED. Here we describe a novel missense mutation, c.367G>A (p.Asp123Asn), in this gene which did not appear to influence the interaction between EDAR and EDARADD proteins, but led to an impaired ability to activate NF-κB signaling. Female members of the affected family showed either unilateral or bilateral amazia. In addition, an affected girl developed bilateral ovarian teratomas, possibly associated with her genetic condition.
少汗型外胚层发育不良（HED）是一种罕见的疾病，其特征是源自外胚层的结构发育缺陷，包括毛发、指甲、汗腺和牙齿。由EDA、EDAR或EDARADD基因突变引起的HED类型可能表现出几乎相同的表型，这可通过共同的信号通路来解释。这三个基因编码的蛋白质之间的适当相互作用对于激活NF-κB信号通路和随后靶基因的转录很重要。EDARADD基因突变在HED中最罕见。在此，我们描述了该基因中的一种新的错义突变，c.367G>A（p.Asp123Asn），该突变似乎不影响EDAR与EDARADD蛋白之间的相互作用，但导致激活NF-κB信号的能力受损。受影响家族的女性成员表现为单侧或双侧无乳房。此外，一名受影响的女孩患上了双侧卵巢畸胎瘤，这可能与其遗传状况有关。
