Distinct impacts of bi-allelic WNT10A mutations on the permanent and primary dentitions in odonto-onycho-dermal dysplasia
Distinct impacts of bi-allelic WNT10A mutations on the permanent and primary dentitions in odonto-onycho-dermal dysplasia
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双等位基因 WNT10A 突变对牙甲真皮发育不良恒牙列和乳牙列的不同影响
DOI：
10.1002/ajmg.a.60682
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发表时间：
2019-01-01
影响因子：
2
通讯作者：
Feng, Hailan
中科院分区：
文献类型：
--
作者：
Yu, Miao;Liu, Yang;Feng, Hailan
牙-甲-真皮发育不良（OODD）是一种罕见的常染色体隐性遗传综合征，以多发性外胚层异常为特征。无翅型MMTV整合位点家族成员10A（WNT 10A）基因的突变与OODD相关。迄今为止，仅报道了11个OODD相关的WNT 10A突变。在这份报告中，我们描述了四个无关的OODD患者的临床表现，重点是牙齿表型。通过桑格测序，我们在WNT 10 A基因中发现了5个新的突变，包括两个纯合无义突变c.1176C>A（p.Cys392*）和c.742C>T（p.Arg248*），一个纯合移码突变c.898- 899 delAT（p.Ile300Profs*126），以及复合杂合突变c.826T>A（p.Cys276Ser）和c.949delG（p.Ala317Hisfs*121）。我们的研究结果证实了WNT 10A的双等位基因突变是导致OODD的原因，并大大扩展了OODD的突变谱。我们首次证明了双等位基因WNT 10A突变可导致恒牙缺失，这增强了WNT 10A突变的表型谱。有趣的是，我们发现WNT 10 A基因的双等位基因突变优先影响恒牙列而不是乳牙列，这表明WNT 10 A在恒牙和乳牙发育中调节的分子机制可能不同。
Odonto-onycho-dermal dysplasia (OODD) is a rare autosomal recessive syndrome characterized by multiple ectodermal abnormalities. Mutations of the wingless-type MMTV integration site family member 10A (WNT10A) gene have been associated with OODD. To date, only 11 OODD-associated WNT10A mutations have been reported. In this report, we Characterized the clinical manifestations with focusing on dental phenotypes in four unrelated OODD patients. By Sanger sequencing, we identified five novel mutations in the WNT10A gene, including two homozygous nonsense mutations c.1176C>A (p.Cys392*) and c.742C>T (p.Arg248*), one homozygous frame-shift mutation c.898-899delAT (p.Ile300Profs*126), and a compound heterozygous mutation c.826T>A (p.Cys276Ser) and c.949delG (p.Ala317Hisfs*121). Our findings confirmed that bi-allelic mutations of WNT10A were responsible for OODD and greatly expanded the mutation spectrum of OODD. For the first time, we demonstrated that bi-allelic WNT10A mutations could lead to anodontia of permanent teeth, which enhanced the phenotypic spectrum of WNT10A mutations. Interestingly, we found that bi-allelic mutations in the WNT10A gene preferentially affect the permanent dentition rather the primary dentition, suggesting that the molecular mechanisms regulated by WNT10A in the development of permanent teeth and deciduous teeth might be different.