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. The purpose of this study was to identify BCOR mutations in two OFCD patients, if it present, and to clarify the pathogenesis of radiculomegaly using one OFCD patient's pulp and periodontal ligament (PDL) cells. In our genetic analysis, two novel BCOR mutations were found. We also examined the transcript levels and the effects of NMD using cultured pulp and PDL cells from one affected patient. BCOR expression was normal in pulp but reduced in PDL cells, which is consistent with the higher rates of NMD in PDL cells. The mutant PDL cells had unstable mutant transcripts and proliferated faster than did wild-type cells, but mutant pulp cells appeared normal by these measures. In summary, 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.
a b s t r a c tMutations in the BCL-6 corepressor (BCOR) gene, which encodes a transcriptional corepressor, were described to cause oculofaciocardiodental syndrome (MIM 300166). The purpose of this study was to localize the classical nuclear localization signals (NLSs) of the BCOR using reported human BCOR mutations with comparable phenotypes. The genotype-phenotype correlation among the mutations could not be clearly explained; however, the classical NLSs were identified at two possible sites; RVDRKRKVSGD at aa1131-1141 (NLS1) and LKAKRRRVSK at aa1158-1167 (NLS2). In addition, according to our results, NLS2 displayed a more efficient nuclear import function than NLS1.
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