Center of Excellence in Genomics and Precision Dentistry, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Oral Dis. 2024 Mar;30(2):537-550. doi: 10.1111/odi.14510. Epub 2023 Feb 5.
To identify etiologic variants and perform deep dental phenotyping in patients with amelogenesis imperfecta (AI).
Three patients of two unrelated families were evaluated. Genetic variants were investigated by exome and Sanger sequencing. An unerupted permanent third molar (AI1) from Patient1 and a deciduous first molar (AI2) from Patient2, along with three tooth-type matched controls for each were characterized.
All three patients harbored biallelic pathogenic variants in FAM20A, indicating AI1G. Of the four identified variants, one, c.1231C > T p.(Arg411Trp), was novel. Patient1 possessed the largest deletion, 7531 bp, ever identified in FAM20A. In addition to hypoplastic enamel, multiple impacted teeth, intrapulpal calcification, pericoronal radiolucencies, malocclusion, and periodontal infections were found in all three patients, gingival hyperplasia in Patient1 and Patient2, and alveolar bone exostosis in Patient3. Surface roughness was increased in AI1 but decreased in AI2. Decreased enamel mineral density, hardness, and elastic modulus were observed in AI1 enamel and dentin and AI2 dentin, along with decreased phosphorus, increased carbon, and increased calcium/phosphorus and carbon/oxygen ratios. Severely collapsed enamel rods and disorganized dentin-enamel junction were observed.
We report a novel FAM20A variant and, for the first time, the defective mineral composition and physical/mechanical properties of AI1G teeth.
鉴定成釉不全（AI）患者的病因变体并进行深度牙齿表型分析。
评估了两个不相关家族的 3 名患者。通过外显子组和 Sanger 测序研究遗传变异。对患者 1 的一颗未萌出的第三恒磨牙（AI1）和患者 2 的一颗乳磨牙（AI2）以及每颗牙齿的三个牙型匹配的对照牙齿进行了特征分析。
所有 3 名患者均携带双等位基因致病性变体 FAM20A，表明 AI1G。在鉴定的 4 个变体中，有一种 c.1231C > T p.(Arg411Trp) 是新的。患者 1 携带 FAM20A 中从未报道过的最大缺失，为 7531bp。除了釉质发育不全外，所有 3 名患者还发现了多个埋伏牙、牙髓内钙化、冠周透亮区、错颌畸形和牙周感染，患者 1 和患者 2 还出现了牙龈增生，患者 3 出现了牙槽骨外生骨。AI1 的表面粗糙度增加，但 AI2 的表面粗糙度降低。AI1 釉质和牙本质以及 AI2 牙本质中的釉质矿物质密度、硬度和弹性模量降低，同时磷降低，碳增加，钙/磷和碳/氧比值增加。观察到严重塌陷的釉柱和紊乱的牙釉质-牙本质交界处。
我们报告了一种新型 FAM20A 变体，以及首次发现 AI1G 牙齿的缺陷矿物质组成和物理/机械性能。
