Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
Department of Molecular Genetics & Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Korea.
Oral Dis. 2018 Sep;24(6):1037-1041. doi: 10.1111/odi.12859. Epub 2018 Jun 8.
To identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility, and root resorption.
DNA samples were collected from a trio of family members, and whole-exome sequencing was performed.
Mutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C-terminus, escaping from the nonsense-mediated decay system. Sanger sequencing confirmed that this mutation was generated spontaneously.
In this study, we identified a novel nonsense mutation in the last exon of the NOTCH2 gene causing Hajdu-Cheney syndrome. We described the genotype and phenotype correlation and the related dental complications. These results will advance the understanding of the NOTCH2 signaling in periodontitis and root resorption.
鉴定一位具有面部畸形、牙齿异常松动和牙根吸收的个体的分子遗传病因。
收集一家三口的 DNA 样本，并进行全外显子组测序。
突变分析显示 NOTCH2 基因最后一个外显子中存在一个新生突变（c.6787C>T）。该突变将引入一个提前终止密码子[p.(Gln2263*)]，并产生一个没有 C 末端的截短蛋白，逃避无义介导的衰变系统。Sanger 测序证实该突变是自发产生的。
在这项研究中，我们在 NOTCH2 基因的最后一个外显子中发现了一个新的无义突变，导致 Hajdu-Cheney 综合征。我们描述了基因型和表型的相关性以及相关的牙科并发症。这些结果将有助于深入了解 NOTCH2 信号在牙周炎和牙根吸收中的作用。
