Department of Pediatric Dentistry, Stomatological Hospital of Tianjin Medical University, Tianjin, China.
Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Orthod Craniofac Res. 2021 May;24(2):233-240. doi: 10.1111/ocr.12424. Epub 2020 Sep 10.
The aim of this study was to explore the genetic basis of non-syndromic tooth agenesis (TA) in a Chinese family of five individuals using whole-exome sequencing (WES) analysis.
Five participants/Family-based study of a non-syndromic TA proband.
The proband, proband's mother and grandmother displayed congenital tooth deficiency. Genomic DNA was extracted from the peripheral blood or saliva samples of the proband, her parents and her grandmother, and WES was utilized to identify the causal genetic mutation. The identified mutation was further verified by Sanger sequencing and analysed using bioinformatics tools.
A novel missense mutation, c.G711T (p.L237F), was identified in the low-density lipoprotein receptor-related protein 6 (LRP6) gene in all affected individuals. Bioinformatics analysis predicted the mutation to be deleterious, with the mutant LRP6 protein displaying a tertiary structural change that might disturb the Wnt/β-catenin signalling pathway.
The identification of the mutation in the LRP6 gene and autosomal dominant inheritance with TA in the generations is consistent with the mutation being responsible for TA in the family, and furthers the association of LRP6 with nonsyndromic TA.
本研究旨在通过全外显子组测序（WES）分析，探讨一个五名中国个体的非综合征性牙齿缺失（TA）的遗传基础。
五名参与者/非综合征性 TA 先证者的家系研究。
从先证者、先证者的母亲和祖母的外周血或唾液样本中提取基因组 DNA，并进行 WES 以鉴定致病的遗传突变。通过 Sanger 测序进一步验证所鉴定的突变，并使用生物信息学工具进行分析。
在所有受影响的个体中，低密度脂蛋白受体相关蛋白 6（LRP6）基因中发现了一个新的错义突变 c.G711T（p.L237F）。生物信息学分析预测该突变具有有害性，突变型 LRP6 蛋白显示出三级结构变化，可能干扰 Wnt/β-catenin 信号通路。
LRP6 基因中的突变以及与 TA 相关的常染色体显性遗传与家族中的 TA 一致，进一步证实了 LRP6 与非综合征性 TA 的关联。
