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Objectives: To identify etiologic variants and perform deep dental phenotyping in patients with amelogenesis imperfecta (AI). Methods: 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. Results: 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. Conclusions: We report a novel FAM20A variant and, for the first time, the defective mineral composition and physical/mechanical properties of AI1G teeth. [ABSTRACT FROM AUTHOR]

Objectives: Autosomal‐dominant hypocalcified amelogenesis imperfecta (ADHCAI) shows phenotypic heterogeneity. Our aim was to characterise the ADHCAI phenotypes, tooth properties and genotypes. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]