Only Four Genes (EDA1, EDAR, EDARADD, and WNT10A) Account for 90% of Hypohidrotic/Anhidrotic Ectodermal Dysplasia Cases
Only Four Genes (EDA1, EDAR, EDARADD, and WNT10A) Account for 90% of Hypohidrotic/Anhidrotic Ectodermal Dysplasia Cases
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DOI：
10.1002/humu.21384
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发表时间：
2011-01-01
期刊：
影响因子：
3.9
通讯作者：
Smahi, Asma
中科院分区：
文献类型：
--
作者：
Cluzeau, Celine;Hadj-Rabia, Smail;Smahi, Asma
少汗性和无汗性外胚层发育不良 (HED/EDA) 是一种罕见的遗传性皮肤病，其特征是汗腺、牙齿和毛发发育异常。迄今为止，已鉴定出三种致病基因，即（1）EDA1，导致X连锁形式，（2）EDAR，和（3）EDARADD，导致常染色体显性和隐性形式。最近，WNT10A 基因被确定与各种常染色体隐性遗传形式的外胚层发育不良有关，包括甲齿胚发育不良 (OODD) 和 Schopf-Schulz-Passarge 综合征。我们系统地研究了 65 名无关患者的大队列中的 EDA1、EDAR、EDARADD 和 WNT10A 基因，其中 61 名患者患有 HED/EDA。总共 50 个突变（包括 32 个新突变）占我们系列病例的 60/65。这四种基因占 HED/EDA 病例的 92%（56/61 例患者）：（1）EDA1 基因是最常见的致病基因（占病例的 58%），（2）WNT10A 和 EDAR 各占 16% 的病例。此外，显性 HED/EDA 的一个新疾病位点映射到染色体 14q12-q13.1。虽然携带 EDA1、EDAR 或 EDARADD 突变的患者之间没有临床差异，但携带 WNT10A 突变的患者表现出独特的临床特征（明显的牙齿表型，无面部畸形），有助于决定在 HED/EDA 中应首先研究哪个基因。 Hum Mutat 32:70-77, 2011。(C) 2010 Wiley-Liss, Inc.
Hypohidrotic and anhidrotic ectodermal dysplasia (HED/EDA) is a rare genodermatosis characterized by abnormal development of sweat glands, teeth, and hair. Three disease-causing genes have been hitherto identified, namely, (1) EDA1 accounting for X-linked forms, (2) EDAR, and (3) EDARADD, causing both autosomal dominant and recessive forms. Recently, WNT10A gene was identified as responsible for various autosomal recessive forms of ectodermal dysplasias, including onycho-odontodermal dysplasia (OODD) and Schopf-Schulz-Passarge syndrome. We systematically studied EDA1, EDAR, EDARADD, and WNT10A genes in a large cohort of 65 unrelated patients, of which 61 presented with HED/EDA. A total of 50 mutations (including 32 novel mutations) accounted for 60/65 cases in our series. These four genes accounted for 92% (56/61 patients) of HED/EDA cases: (1) the EDA1 gene was the most common disease-causing gene (58% of cases), (2) WNT10A and EDAR were each responsible for 16% of cases. Moreover, a novel disease locus for dominant HED/EDA mapped to chromosome 14q12-q13.1. Although no clinical differences between patients carrying EDA1, EDAR, or EDARADD mutations could be identified, patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism), helping to decide which gene should be first investigated in HED/EDA. Hum Mutat 32:70-77, 2011. (C) 2010 Wiley-Liss, Inc.