期刊
CYTOGENETIC AND GENOME RESEARCH
卷 100, 期 1-4, 页码 124-128出版社
KARGER
DOI: 10.1159/000072846
关键词
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资金
- NICHD NIH HHS [HD40661] Funding Source: Medline
Fragile X syndrome is a trinucleotide repeat disorder in which a (CGG)(n) element located within the 5' untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene expands to more than 200 copies (full mutation) and becomes hypermethylated. Such expansions are accompanied by the failure to produce FMR1 protein (FMRP), resulting in the fragile X phenotype. For smaller (premutation) expansions (similar to 55-200 repeats), FMR1 mRNA and FMRP levels had been assumed to be normal; however, our group and others have recently demonstrated that FMR I mRNA levels are elevated in cells harboring premutation alleles. Moreover, mRNA levels remain elevated in fragile X males with partially methylated full mutation alleles. Finally,some fragile X males with hyper-methylated, full mutation alleles continue to produce FMR1 mRNA, despite the expectation that those genes should be silent. These observations all point to a complex mechanism of expression of the FMR1 gene, one that provides a more consistent foundation for the spectrum of clinical involvement. An FMRP deficit is observed in all categories of fragile X individuals, including carriers of the premutation and partially methylated full mutation alleles. These results demonstrate that lowered FMRP levels, in the absence of methylation-coupled silencing of the FMR I gene, are not caused by reduced transcriptional activity, but rather by a reduced efficiency of translation. Copyright (C) 2002 S. Karger AG, Basel.
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