Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Dermatology. 2011;223(1):74-9. doi: 10.1159/000330557. Epub 2011 Aug 29.
Hypohidrotic ectodermal dysplasia (HED) is a rare condition characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X-linked recessive, autosomal-dominant or autosomal-recessive inheritance trait. X-linked form of HED is caused by mutations in the EDA gene, while autosomal forms are caused by mutations in either EDAR or EDARADD genes.
We analyzed the DNA from a Japanese patient with HED through direct sequencing, and also performed functional studies for the mutation.
We identified a homozygous missense mutation c.1073G>A (p.R358Q) in the EDAR gene of the patient, which was a nonconservative amino acid substitution within the death domain of EDAR protein. We demonstrated that the p.R358Q mutant EDAR protein lost its affinity to EDARADD, leading to reduced activation of the downstream NF-κB.
Our data further suggest the crucial role of the EDAR signaling in development of hair, teeth, and sweat gland in humans.
少汗型外胚层发育不全症（HED）是一种罕见的疾病，其特征为毛发稀疏、少汗和牙齿缺失。该疾病具有 X 连锁隐性、常染色体显性或常染色体隐性遗传特征。X 连锁形式的 HED 是由 EDA 基因突变引起的，而常染色体形式则是由 EDAR 或 EDARADD 基因突变引起的。
我们通过直接测序分析了一位 HED 日本患者的 DNA，并对该突变进行了功能研究。
我们在患者的 EDAR 基因中发现了一个纯合错义突变 c.1073G>A（p.R358Q），这是 EDAR 蛋白死亡结构域内的非保守氨基酸取代。我们证明，p.R358Q 突变的 EDAR 蛋白失去了与 EDARADD 的亲和力，导致下游 NF-κB 的激活减少。
我们的数据进一步表明 EDAR 信号在人类毛发、牙齿和汗腺发育中的关键作用。
