[Experimental therapy: reactivation of the FMR1 gene involved in fragile X syndrome].
Fragile X syndrome represents the most common inherited cause of mental retardation worldwide. Fragile X belongs to a large group of more than 200 mental retardation conditions caused by mutations in X-linked genes (XLMR), that have a collective frequency of up to 1 in 1000 males. Fragile X syndrome is also unique because it was the first genetic condition caused--in the overwhelming majority of cases--by the expansion of an unstable CGG repeat, becoming the prototype of a growing list of inherited disorders due to the instability of trinucleotide repeats. Ten years after the cloning of the FMR1 gene involved in fragile X syndrome, we still don't know all the molecular players that allow the destabilization of the CGG repeat located close to the gene's CpG island. However, the finding of a founder effect in fragile X syndrome indicates that only few of the unstable repeats eventually reached the pathological range. The line of research was aimed at understanding what happens after the fragile X mutation has reached a pathological size. What we showed with our 'reactivation' experiments is that the size of the CGG expansion per se does not cause the silencing of the FMR1 gene: it's the methylation that is added to the expansion that leads to the transcriptional block. Thus, by studying the 'reactivation' of fragile X full mutations, we try to learn more about their 'inactivation' and--hopefully--about possible ways of preventing or 'reverting' their inactivation in fragile X children.
Chiurazzi
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P
Department of Pediatrics, University Hospital, Messina, Italy. pietrosmile@yahoo.com
Neri
G
G
D002648:Child; D002873:Chromosome Fragility; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics* / Q000628:therapy*; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018911:Trinucleotide Repeats
D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C497683:FMR1 protein, human