Novel FAM20A mutations in hypoplastic amelogenesis imperfecta

✍ Scribed by Sang Hyun Cho; Figen Seymen; Kyung-Eun Lee; Sook-Kyung Lee; Young-Sun Kweon; Kyung Jin Kim; Seung-Eun Jung; Su Jeong Song; Mine Yildirim; Merve Bayram; Elif Bahar Tuna; Koray Gencay; Jung-Wook Kim

• Book ID: 102261331
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 276 KB
• Volume: 33
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.21621

✦ Synopsis

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.