[Experimental therapy: reactivation of the FMR1 gene involved in fragile X syndrome].

Abstract

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.

• Authors: P Chiurazzi, G Neri
• Journal: Revista de neurologia (Rev Neurol) Vol. 33 Suppl 1 Pg. S62-5 (Oct 2001) ISSN: 0210-0010 [Print] Spain
• Vernacular Title: Investigación terapéutica: reactivación del gen FMR1 causante del síndrome X frágil.
• PMID: 12447822 (Publication Type: English Abstract, Journal Article)

Chemical References

• FMR1 protein, human
• Nerve Tissue Proteins
• RNA-Binding Proteins
• Fragile X Mental Retardation Protein

Topics

• Child
• Chromosome Fragility
• Fragile X Mental Retardation Protein
• Fragile X Syndrome (genetics, therapy)
• Gene Expression Regulation
• Genetic Therapy
• Humans
• Male
• Mutation
• Nerve Tissue Proteins (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)
• Trinucleotide Repeats