| Abstract: |
The fragile-X syndrome is one of the most common forms of inherited mental retardation and the second most common cause of mental retardation after Down syndrome. It is inherited as an X-linked form of mental retardation, hence the excess of affected males in families with FXS.In 1991, the molecular basis of fragile-X syndrome was revealed and shown to be associated with a massive trinucleotide repeat expansion (CGG) within the fragile-X mental retardation-1 (FMR1) gene. This CGG trinucleotide repeat is located in the 5 end of the first exon of the FMR1 gene, 250 bp distal to a CpG island: a dinucleotide repeat region very rich in CG, containing rare restriction sites and is methylated.The number of CGG repeat units is polymorphic in normal individuals (5-50 repeats) with an average of 30 repeats. Carrier males and females have repeat numbers of 50-200 repeats, an expansion referred to as ”permutation”, which in most cases is not associated with the disorder phenotype. In affected individuals, the CGG repeats are amplified to more than 200 repeats and the CpG island is abnormally hypermethylated. This second mutation type is called ”full mutation”..
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