Yu Shunlan, Liu Dandan, Yan Changqing, Yuan Chao, Zhang Chenying, Zheng Shuguo
Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, PR China.
Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices & Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials, Beijing, PR China.
Arch Oral Biol. 2024 Aug;164:105991. doi: 10.1016/j.archoralbio.2024.105991. Epub 2024 May 8.
To identify the genetic cause of a Chinese family with hypomaturation amelogenesis imperfecta (AI) and to characterize the structure of GPR68 mutated enamel in order to develop a deeper understanding of the role of the GPR68 protein during the intricate process of amelogenesis.
One Chinese family with generalized hypomaturation AI was recruited. Two of the third molars from the proband were subjected to scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Whole exome sequencing (WES) was performed, and the identified mutation was confirmed by Sanger sequencing. Bioinformatics studies were further conducted to analyze the potential deleterious effects of the mutation.
The proband presented with a hypomaturation AI phenotype, characterized by fragile and discolored enamel surface. The AI enamel showed prismatic structure, which was sporadically obscured by areas of amorphous material and porous structure. EDX analysis showed the proband's enamel demonstrated a significant decrease in calcium and phosphorus content and a significant increase in oxygen compared with normal enamel. A novel homozygous mutation of G protein-coupled receptor 68 (GPR68) (c .149 T > A, p.Ile50Asn) was identified in the proband. Bioinformatics analysis indicated that the mutation site displayed a high level of evolutionary conservation among species, and the mutation might impact the stability and conformation of the protein.
The novel homozygous GPR68 mutation resulted in hypomaturation AI. We first described the effect of GPR68 mutation on enamel structure. Our results provide new genetic evidence that mutations involved in GPR68 contribute to hypomaturation AI.
确定一个患有低成熟型牙釉质发育不全（AI）的中国家庭的遗传病因，并对GPR68突变牙釉质的结构进行表征，以便更深入地了解GPR68蛋白在复杂的牙釉质形成过程中的作用。
招募了一个患有全身性低成熟型AI的中国家庭。对先证者的两颗第三磨牙进行扫描电子显微镜（SEM）和能量色散X射线光谱（EDX）分析。进行全外显子组测序（WES），并通过桑格测序确认所鉴定的突变。进一步进行生物信息学研究，以分析该突变的潜在有害影响。
先证者表现出低成熟型AI表型，其特征为牙釉质表面脆弱且变色。AI牙釉质呈现棱柱结构，偶尔被无定形物质区域和多孔结构所掩盖。EDX分析显示，与正常牙釉质相比，先证者的牙釉质中钙和磷含量显著降低，氧含量显著增加。在先证者中鉴定出一种新的G蛋白偶联受体68（GPR68）纯合突变（c.149 T>A，p.Ile50Asn）。生物信息学分析表明，该突变位点在物种间具有高度的进化保守性，该突变可能会影响蛋白质的稳定性和构象。
新的GPR68纯合突变导致了低成熟型AI。我们首次描述了GPR68突变对牙釉质结构的影响。我们的结果提供了新的遗传证据，表明涉及GPR68的突变导致了低成熟型AI。
