WNT10A Mutations Are a Frequent Cause of a Broad Spectrum of Ectodermal Dysplasias with Sex-Biased Manifestation Pattern in Heterozygotes
WNT10A Mutations Are a Frequent Cause of a Broad Spectrum of Ectodermal Dysplasias with Sex-Biased Manifestation Pattern in Heterozygotes
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DOI：
10.1016/j.ajhg.2009.06.001
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发表时间：
2009-07-10
影响因子：
9.8
通讯作者：
Roepke, Albrecht
中科院分区：
文献类型：
--
作者：
Bohring, Axel;Stamm, Thomas;Roepke, Albrecht
齿-甲-真皮发育不良（OODD）是一种罕见的常染色体隐性遗传形式的外胚层发育不良，包括严重的少齿症，指甲营养不良，掌跖角化过度和多汗症，最近被证明是由纯合无义WNT 10A突变引起的三个黎巴嫩血缘家庭。在这里，我们报告了12例患者，来自I I无关的家庭，与外胚层发育不良引起的五个以前未描述的WNT 10A突变。在这项研究中，我们发现（1）VMT 10 A突变不仅导致OODD，而且还导致其他形式的外胚层发育不良，从明显单一症状的严重少牙到Schopf-Schulz-Passarge综合征，迄今为止，Schopf-Schulz-Passarge综合征被认为是一个独特的实体，其发现沿着眼睑边缘的许多囊肿和良性和恶性皮肤肿瘤的风险增加;（2）WNT 10A突变是外胚层发育不良的常见原因，在约9%的外胚层发育不良患者队列中发现;（3）约一半的杂合子（53.8%）表现为表型异常，主要为牙、甲异常，在OODD中未见报道;（4）杂合子表现出性别偏向的表现模式，男性牙齿异常的比例显著高于女性，这可能暗示了WNT 10A表达的性别特异性差异。
Odonto-onycho-dermal dysplasia (OODD), a rare autosomal-recessive inherited form of ectodermal dysplasia including severe oligodontia, nail dystrophy, palmoplantar hyperkeratosis, and hyperhidrosis, was recently shown to be caused by a homozygous nonsense WNT10A mutation in three consanguineous Lebanese families. Here, we report on 12 patients, from I I unrelated families, with ectodermal dysplasia caused by five previously undescribed WNT10A mutations. In this study, we show that (1) VMT10A mutations cause not only OODD but also other forms of ectodermal dysplasia, reaching from apparently monosymptomatic severe oligodontia to Schopf-Schulz-Passarge syndrome, which is so far considered a unique entity by the findings of numerous cysts along eyelid margins and the increased risk of benign and malignant skin tumors; (2) WNT10A mutations are a frequent cause of ectodermal dysplasia and were found in about 9% of an unselected patient cohort; (3) about half of the heterozygotes (53.8%) show a phenotype manifestation, including mainly tooth and nail anomalies, which was not reported before in OODD; and (4) heterozygotes show a sex-biased manifestation pattern, with a significantly higher proportion of tooth anomalies in males than in females, which may implicate gender-specific differences of WNT10A expression.