EDARADD 基因突变占少部分少汗型外胚层发育不全病例。

Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases.

机构信息

INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300 France.

出版信息

Br J Dermatol. 2010 May;162(5):1044-8. doi: 10.1111/j.1365-2133.2010.09670.x. Epub 2010 Mar 5.

DOI:10.1111/j.1365-2133.2010.09670.x

PMID:20222921

Abstract

BACKGROUND

Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair and teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal dominant and recessive forms occasionally occur and result from mutations in at least two other genes: EDAR and EDARADD. EDARADD interacts with the TAB2/TRAF6/TAK1 complex, which is necessary for NF-kappaB activation by EDAR.

OBJECTIVES

To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED.

MATERIALS AND METHODS

We have screened 28 familial or sporadic HED cases with no mutations in the EDA and EDAR genes for EDARADD, TRAF6, TAB2 and TAK1 mutations.

RESULTS

We identified one EDARADD 6-bp homozygous in-frame deletion (c.402-407del, p.Thr135-Val136del) in a patient born to consanguineous parents. Functional studies showed that the p.Thr135-Val136del impaired the EDAR-EDARADD interaction and then severely inhibited NF-kappaB activity. In the remaining 27 patients, we failed to find causative mutations in EDARADD, or in TRAF6, TAB2 or TAK1.

CONCLUSIONS

Our study demonstrates that EDARADD mutations are not a frequent cause of HED, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease.

摘要

背景

少汗型外胚层发育不良（HED）的特征是外分泌汗腺、毛发和牙齿发育异常。该病的 X 连锁形式是由 EDA 基因突变引起的，占 HED 病例的大多数。常染色体显性和隐性形式也偶尔发生，是由至少另外两个基因的突变引起的：EDAR 和 EDARADD。EDARADD 与 TAB2/TRAF6/TAK1 复合物相互作用，该复合物对于 EDAR 激活 NF-κB 是必需的。

目的

确定 HED 中 EDARADD、TRAF6、TAB2 和 TAK1 突变的频率。

材料和方法

我们已经筛选了 28 个家族性或散发性 HED 病例，这些病例在 EDA 和 EDAR 基因中没有突变，以寻找 EDARADD、TRAF6、TAB2 和 TAK1 突变。

结果

我们在一名出生于近亲的患者中发现了一个 EDARADD 的 6 个碱基对的纯合框内缺失（c.402-407del，p.Thr135-Val136del）。功能研究表明，p.Thr135-Val136del 损害了 EDAR-EDARADD 相互作用，然后严重抑制了 NF-κB 活性。在其余 27 名患者中，我们未能在 EDARADD 或 TRAF6、TAB2 或 TAK1 中发现致病突变。