Department of Second Dental Center, Ninth People's Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
Department of Oral Implantology, Ninth People's Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai Key Laboratory of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
Clin Genet. 2022 Dec;102(6):503-516. doi: 10.1111/cge.14225. Epub 2022 Sep 17.
Tooth agenesis is a high genetic heterogeneous disorder with more than 80 genes identified as associated molecular causes. The present study aimed to detect the possible pathogenic variants in a cohort of well-characterized probands with a clinical diagnosis of tooth agenesis. We performed whole-exome sequencing (WES) in 131 tooth agenesis patients with no previously identified molecular diagnosis. All the potential pathogenic variants were verified by Sanger sequencing in patients and their family members. Seventy-three patients were genetically diagnosed in 131 unrelated Chinese patients with tooth agenesis, providing a positive molecular diagnostic rate of 55.7%, including 53.8% (49/91) in the non-syndromic tooth agenesis (NSTA) group, and 60.0% (24/40) in syndromic tooth agenesis (STA) group. A total of 75 variants from 13 different genes were identified, including 33 novel variants, and WNT10A and EDA are the most common causative genes associated with non-syndromic and syndromic tooth agenesis, respectively. This study further extends the variant spectrum and clinical profiles of tooth agenesis, which has a positive significance for clinical practice, genetic diagnosis, prenatal counseling and future treatment.
牙齿缺失是一种高度遗传异质性疾病，已有 80 多个基因被确定为相关的分子病因。本研究旨在检测一组具有牙齿缺失临床诊断的特征明确的先证者中可能的致病变异。我们对 131 名无先前确定分子诊断的牙齿缺失患者进行了全外显子组测序（WES）。所有潜在的致病性变异均通过 Sanger 测序在患者及其家庭成员中进行了验证。在 131 名无关的中国牙齿缺失患者中，有 73 名患者被遗传诊断，阳性分子诊断率为 55.7%，其中非综合征性牙齿缺失（NSTA）组为 53.8%（49/91），综合征性牙齿缺失（STA）组为 60.0%（24/40）。共鉴定出 13 个不同基因的 75 个变异，包括 33 个新变异，WNT10A 和 EDA 分别是与非综合征性和综合征性牙齿缺失相关的最常见的致病基因。本研究进一步扩展了牙齿缺失的变异谱和临床特征，对临床实践、遗传诊断、产前咨询和未来治疗具有积极意义。
