Abstract：
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
目的：确定一个中国家族牙釉质发育不全（AI）的遗传原因，并表征GPR68突变牙釉质的结构，以加深对GPR68蛋白在牙釉质形成过程中的作用的认识。
方法：招募了一个患有广泛性增殖性AI的中国家庭。对来自先证者的第三磨牙中的两个进行扫描电子显微镜（SEM）和能量色散X射线光谱（EDX）。进行全外显子组测序（WES），鉴定的突变通过Sanger测序证实。进一步进行生物信息学研究以分析突变的潜在有害作用。
结果：先证者表现为AI表型，其特点是脆弱和变色的搪瓷表面。AI搪瓷呈棱柱形结构，偶尔被无定形材料和多孔结构的区域所掩盖。EDX分析显示，与正常牙釉质相比，先证者牙釉质的钙和磷含量显着降低，氧含量显着增加。G蛋白偶联受体68（GPR68）的新纯合突变（c.149T>A，p.Ile50Asn)在先证中鉴定。生物信息学分析表明，突变位点在物种之间表现出高度的进化保守性，突变可能会影响蛋白质的稳定性和构象。
结论：新的纯合GPR68突变导致AI增殖不足。我们首先描述了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GPR68中涉及的突变有助于AI增殖性降低。
方法：招募了一个患有广泛性增殖性AI的中国家庭。对来自先证者的第三磨牙中的两个进行扫描电子显微镜（SEM）和能量色散X射线光谱（EDX）。进行全外显子组测序（WES），鉴定的突变通过Sanger测序证实。进一步进行生物信息学研究以分析突变的潜在有害作用。
结果：先证者表现为AI表型，其特点是脆弱和变色的搪瓷表面。AI搪瓷呈棱柱形结构，偶尔被无定形材料和多孔结构的区域所掩盖。EDX分析显示，与正常牙釉质相比，先证者牙釉质的钙和磷含量显着降低，氧含量显着增加。G蛋白偶联受体68（GPR68）的新纯合突变（c.149T>A，p.Ile50Asn)在先证中鉴定。生物信息学分析表明，突变位点在物种之间表现出高度的进化保守性，突变可能会影响蛋白质的稳定性和构象。
结论：新的纯合GPR68突变导致AI增殖不足。我们首先描述了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GPR68中涉及的突变有助于AI增殖性降低。
