A novel PITX2 mutation in non-syndromic orodental anomalies
A novel PITX2 mutation in non-syndromic orodental anomalies
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DOI：
10.1111/odi.12804
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发表时间：
2018-05-01
期刊：
影响因子：
3.8
通讯作者：
Shotelersuk, V.
中科院分区：
文献类型：
--
作者：
Intarak, N.;Theerapanon, T.;Shotelersuk, V.
目的确定一个家庭的影响与非综合征orodental anomalies.Subjects和MethodsPhysical和口腔功能的特点orodental的特点和遗传病因。DNA是从一个受影响的泰国家庭收集的。采用全外显子组测序技术鉴定与遗传性口腔畸形相关的致病性变异。桑格sequencing.ResultsWe观察到独特的orodental表现，包括oligodontia，保留乳牙，taurodont磨牙，桩形上颌中切牙，高附加系带结节和中线间隙的先证者和她的母亲。突变分析显示，一个新的杂合移码缺失，c.573_574delCA，p.L193QfsX5，在PITX 2A的外显子5在受影响的家庭成员。定位于PITX 2的C-末端的转录激活结构域2中的氨基酸改变在进化上是保守的。PITX 2的突变与常染色体显性遗传的Axenomy-Rieger综合征和非综合征性眼异常有关，但从未发现引起孤立的口腔异常。我们建议，在C-末端结构域的PITX 2的特定位置是牙齿发育所必需的。
ObjectiveTo identify orodental characteristics and genetic aetiology of a family affected with non-syndromic orodental anomalies.Subjects and MethodsPhysical and oral features were characterised. DNA was collected from an affected Thai family. Whole-exome sequencing was employed to identify the pathogenic variants associated with inherited orodental anomalies. The presence of the identified mutation was confirmed by Sanger sequencing.ResultsWe observed unique orodental manifestations including oligodontia, retained primary teeth, taurodont molars, peg-shaped maxillary central incisors, high attached frenum with nodule and midline diastema in the proband and her mother. Mutation analyses revealed a novel heterozygous frameshift deletion, c.573_574delCA, p.L193QfsX5, in exon 5 of PITX2A in affected family members. The amino acid alterations, localised in the transcriptional activation domain 2 in the C-terminus of PITX2, were evolutionarily conserved. Mutations in PITX2 have been associated with autosomal-dominant Axenfeld-Rieger syndrome and non-syndromic eye abnormalities, but never been found to cause isolated oral anomalies.ConclusionsThis study for the first time demonstrates that the PITX2 mutation could lead to non-syndromic orodental anomalies in humans. We propose that the specific location in the C-terminal domain of PITX2 is exclusively necessary for tooth development.