Background: Mutations in 6 genes have been identified as being part of the etiology of amelogenesis imperfecta (AI) with various phenotypes in an isolated condition. Among them the FAM83H gene is the major contributor to the etiology of AI with unknown function. Objective: This study aims to determine the phenotypic and molecular characterization of Chinese AI patients and to analyze the structure and function of the FAM83H protein. Methods: We enrolled 6 hypocalcified AI and 3 hypoplastic AI families from the Chinese population. Mutation analysis was performed by amplifying and sequencing all exons including intron-exon borders for FAM83H and ENAM genes. Structural modeling and function analysis on the FAM83H protein were carried out by bioinformatic processing. Results: No obvious anterior open bite was observed in all the investigated individuals. Five mutations (c.906T>G, c.924dupT, c.973C>T, c.1354C>T and c.2029C>T) in the C-terminal of the FAM83H gene were revealed, respectively, in 5 out of 6 hypocalcified AI families, and a splicing mutation c.534 + 1G>A in the ENAM gene was identified in 1 out of 3 hypoplastic AI families. Structural models of the N- and C-terminal regions of FAM83H were generated by homology modeling. The predicted structure of the FAM83H N-terminal shows resemblance to that of glycosyltransferases with GT-A folds, and the predicted structure of the FAM83H C-terminal possesses similarity to type I collagen protein. Conclusions: To our knowledge, this is the first report of AI with specific molecular variations in families of Chinese descent. Our study provides new insights into the structure and function of the FAM83H protein.

Keywords:
Enamel, Amelogenesis imperfecta, FAM83H, Mutation
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2012
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