Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia:: The odonto-onycho-dermal dysplasia
Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia:: The odonto-onycho-dermal dysplasia
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DOI：
10.1086/520064
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发表时间：
2007-10-01
影响因子：
9.8
通讯作者：
Megarbane, Andre
中科院分区：
文献类型：
--
作者：
Adaimy, Lynn;Chouery, Eliane;Megarbane, Andre
齿甲真皮发育不良是一种罕见的常染色体隐性遗传综合征，表现为毛发干燥、牙齿严重发育不全、舌头光滑伴真菌状和丝状乳头明显减少、甲发育不良、手掌和足底角化症和多汗、皮肤角化过度。我们研究了三个近亲黎巴嫩穆斯林什叶派家庭，其中包括六名患有齿甲真皮发育不良的个体。使用纯合性作图策略，我们将疾病位点分配到染色体 2q35-q36.2 上类似于 9-cM 的区域，位于标记 rs16853834 和 D2S353 之间，最大多点 LOD 得分为 5.7。筛选该区域的候选基因使我们识别出相同的 c。所有患者的 WNT10A 基因外显子 3 均出现 697GrT (p. Glu233X) 纯合无义突变。在蛋白质水平上，预计该突变将导致蛋白质过早截短为 232 个氨基酸，而不是 417 个氨基酸。据我们所知，这是第一份关于 WNT10A 突变导致的人类表型的报告，也是首次证明 WNT 信号通路改变引起的外胚层发育不良，从而扩大了 WNT 相关疾病的范围。
Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an similar to 9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c. 697GrT (p. Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases.