Genomics and Precision Dentistry Research Unit, Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Geriatric Dentistry and Special Patients Care Clinic, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Oral Dis. 2022 Apr;28(3):734-744. doi: 10.1111/odi.13780. Epub 2021 Feb 4.
Autosomal-dominant hypocalcified amelogenesis imperfecta (ADHCAI) shows phenotypic heterogeneity. Our aim was to characterise the ADHCAI phenotypes, tooth properties and genotypes.
Three unrelated ADHCAI probands and seven additional affected members of the three families were recruited. Mutations were identified by exome and Sanger sequencing, and haplotypes by SNP array. Tooth colour, roughness, density, nanohardness, minerals and ultrastructure were investigated.
Ten participants were heterozygous for the FAM83H mutation c.1387C>T (p.Gln463*). All shared a 3.43 Mbp region on chromosome 8q24.3 encompassing the FAM83H variant, indicating a common ancestry. The c.1387C>T was estimated to be 23.8 generations or 600 years. The FAM83H enamel had higher roughness and lower lightness, density, nanohardness, and calcium and phosphorus levels than controls. Blunted enamel rods, wide interrod spaces and disorganised dentinoenamel junctions were observed. Evaluating the patients with the same mutation and reviewing others with different mutations in FAM83H revealed that the FAM83H heterogeneous phenotypes are age-influenced. Tooth colour and surface texture change with ageing.
FAM83H enamel demonstrated decreased lightness, density, hardness, calcium, phosphorus and defective ultrastructure. We have identified that the phenotypic variation in FAM83H-associated ADHCAI is age-related. Awareness of the correlation between age and clinical features of FAM83H-ADHCAI can help dentists make an accurate diagnosis.
常染色体显性低钙型牙釉质不全（ADHCAI）表现出表型异质性。本研究旨在描述 ADHCAI 的表型、牙齿特性和基因型。
招募了 3 个无关的 ADHCAI 先证者和这 3 个家系中的另外 7 名受影响成员。通过外显子组和 Sanger 测序鉴定突变，通过 SNP 芯片鉴定单倍型。研究了牙齿颜色、粗糙度、密度、纳米硬度、矿物质和超微结构。
10 名参与者为 FAM83H 突变 c.1387C>T（p.Gln463*）的杂合子。所有参与者都共享 8q24.3 染色体上的一个 3.43 Mbp 区域，该区域包含 FAM83H 变体，表明有共同的祖先。c.1387C>T 估计发生在 23.8 代或 600 年。FAM83H 釉质的粗糙度较高，而亮度、密度、纳米硬度以及钙和磷水平较低。观察到釉柱变钝、间质空间变宽以及牙本质釉质交界处排列紊乱。对具有相同突变的患者进行评估，并回顾其他具有不同 FAM83H 突变的患者，结果表明 FAM83H 异质性表型受年龄影响。牙齿颜色和表面质地随年龄变化而变化。
FAM83H 釉质表现出亮度、密度、硬度、钙、磷降低以及超微结构缺陷。我们已经确定，FAM83H 相关 ADHCAI 的表型变异与年龄有关。了解 FAM83H-ADHCAI 与年龄之间的相关性有助于牙医做出准确诊断。
