title: Novel FAM20A mutations in hypoplastic amelogenesis imperfecta.
abstract: Amelogenesis imperfecta (AI) is a genetically and clinically heterogeneous group of inherited dental enamel defects without any other nonoral symptoms. Recently, a disease-causing nonsense mutation (c.406C>T) in a novel gene, FAM20A, was identified in a large consanguineous family affected by AI with gingival hyperplasia. We performed mutational analyses on nine AI families with similar phenotypes and identified three homozygous mutations (c.34_35delCT, c.813-2A>G, c.1175_1179delGGCTC) in three families and a compound heterozygous mutation (c.[590-2A>G] + [c.826C>T]) in one family. An in vitro splicing assay with a minigene confirmed the mutations located in the splicing acceptor site caused the deletion of exons 3 and 6, respectively. Taking into consideration the locations of the nonsense and frameshift mutations, the mutant transcripts are most likely degraded by nonsense-mediated mRNA degradation and it results in a loss of the FAM20A protein. This study confirms the importance of the FAM20A protein in enamel biomineralization as well as tooth eruption.
authors: Department of Pediatric Dentistry & Dental Research Institute, School of Dentistry, Seoul National University, Chongno-gu, Seoul, Korea.
authors: Sang Hyun
authors: SH
authors: Cho
authors: Figen
authors: F
authors: Seymen
authors: Kyung-Eun
authors: KE
authors: Lee
authors: Sook-Kyung
authors: SK
authors: Lee
authors: Young-Sun
authors: YS
authors: Kweon
authors: Kyung Jin
authors: KJ
authors: Kim
authors: Seung-Eun
authors: SE
authors: Jung
authors: Su Jeong
authors: SJ
authors: Song
authors: Mine
authors: M
authors: Yildirim
authors: Merve
authors: M
authors: Bayram
authors: Elif Bahar
authors: EB
authors: Tuna
authors: Koray
authors: K
authors: Gencay
authors: Jung-Wook
authors: JW
authors: Kim
mesh_terms: D000567:Amelogenesis Imperfecta / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003746:Dental Enamel Proteins / Q000235:genetics*; D005091:Exons; D016368:Frameshift Mutation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D056910:Republic of Korea; D017384:Sequence Deletion
chemical_list: D018389:Codon, Nonsense; D003746:Dental Enamel Proteins; C571509:FAM20A protein, human