Molecular genetic study on root abnormality due to the failure of the RNA program

2015 Fiscal Year Final Research Report

• Project/Area Number: 25463167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OGAWA TAKUYA 東京医科歯科大学, 医歯(薬)学総合研究科, 講師 (50401360)
• Co-Investigator(Kenkyū-buntansha): MORIYAMA Keiji 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (20262206)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: OFCD症候群 / BCOR / 歯根 / 核移行シグナル / ナンセンス変異依存mRNA分解機構

Outline of Final Research Achievements

Oculofaciocardiodental (OFCD) syndrome is a rare X-linked dominant condition. Mutations in BCOR have been described as causal in OFCD syndrome. Almost all BCOR mutations result in premature termination codons (PTCs); therefore, nonsense-mediated mRNA decay (NMD) might have an important role in pathogenesis. In this study, the nonsense and frameshift mutations, which introduce PTCs, were found to contribute to OFCD syndrome in our two patients. Furthermore, in PDL cells, the mutation resulting in a PTC corresponded to greater NMD, unstable mutant transcripts and increased cell proliferation, which may contribute to hyperactive root formation. In addition, we investigated the localization of the classical nuclear localization signals (NLSs) of BCOR gene using the reported human BCOR mutations with comparable phenotypes. The genotype-phenotype correlation among the mutations could not be clearly explained; however, the two classical NLSs were identified at two possible sites.

Free Research Field

医歯薬学