Novel FAM83H mutations in patients with amelogenesis imperfecta

Abstract Amelogenesis imperfecta (AI), characterized by a deficiency in the quantity and/or quality of dental enamel, is genetically heterogeneous and phenotypically variable. The most severe type, hypocalcified AI, is mostly caused by truncating mutations in the FAM83H gene. This study aimed to identify genetic mutations in four Chinese families with hypocalcified AI. We performed mutation analysis by sequencing the candidate FAM83H gene. Three novel mutations (c.931dupC, p.V311Rfs*13; c.1130_1131delinsAA, p.S377X; and c.1147 G > T, p.E383X) and one previously reported mutation (c.973 C > T, p.R325X) in the last exon of FAM83H gene were identified. Furthermore, constructs expressing Green fluorescent protein (GFP)-tagged wild-type and three novel mutant FAM83Hs were transfected into rat dental epithelial cells (SF2 cells). Wild-type FAM83H-GFP was localized exclusively in the cytoplasm, especially in the area surrounding the nucleus, while the mutant FAM83H-GFPs (p.V311Rfs*13, p.S377X, and p.E383X) were localized predominantly in the nucleus, with lower levels in the cytoplasm.