Prasad M K, Laouina S, El Alloussi M, Dollfus H, Bloch-Zupan A
Laboratoire de Génétique Médicale, INSERM U1112, Institut de Génétique Médicale d'Alsace, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg, Strasbourg, France.
Department of Pediatric Dentistry, Faculty of Dental Medicine, Mohammed V University, Rabat, Morocco.
J Dent Res. 2016 Dec;95(13):1457-1463. doi: 10.1177/0022034516663200. Epub 2016 Aug 24.
Amelogenesis imperfecta (AI) is a clinically and genetically heterogeneous group of diseases characterized by enamel defects. The authors have identified a large consanguineous Moroccan family segregating different clinical subtypes of hypoplastic and hypomineralized AI in different individuals within the family. Using targeted next-generation sequencing, the authors identified a novel heterozygous nonsense mutation in COL17A1 (c.1873C>T, p.R625*) segregating with hypoplastic AI and a novel homozygous 8-bp deletion in C4orf26 (c.39_46del, p.Cys14Glyfs*18) segregating with hypomineralized-hypoplastic AI in this family. This study highlights the phenotypic and genotypic heterogeneity of AI that can exist even within a single consanguineous family. Furthermore, the identification of novel mutations in COL17A1 and C4orf26 and their correlation with distinct AI phenotypes can contribute to a better understanding of the pathophysiology of AI and the contribution of these genes to amelogenesis.
牙釉质发育不全（AI）是一组临床和遗传异质性疾病，其特征为牙釉质缺陷。作者发现了一个摩洛哥近亲家庭，该家庭中不同个体存在发育不全型和矿化不足型AI的不同临床亚型。通过靶向新一代测序，作者在COL17A1基因中发现了一个新的杂合无义突变（c.1873C>T，p.R625*），该突变与发育不全型AI共分离，同时在C4orf26基因中发现了一个新的纯合8碱基缺失（c.39_46del，p.Cys14Glyfs*18），该缺失与该家庭中矿化不足-发育不全型AI共分离。这项研究突出了AI的表型和基因型异质性，即使在单个近亲家庭中也可能存在。此外，COL17A1和C4orf26中新突变的鉴定及其与不同AI表型的相关性，有助于更好地理解AI的病理生理学以及这些基因在牙釉质形成中的作用。
