An animal model for fragile X syndrome has been generated, which can be used to study the clinical and biochemical abnormalities caused by absence of FMR1 protein product.
A rapid screening test was developed to detect CGG repeat expansion of the FMR-1 gene causing the fragile X syndrome by a non-radioisotope PCR technique.
The FXR proteins are associated with 60S ribosomal subunits even in cells that lack FMR1 and that are derived from a fragile X syndrome patient, indicating that FMR1 is not required for this association.
Our study supports the idea that major FMR-I gene expansion detectable with Southern hybridization is rare in cytogenetically normal mentally retarded males, including those with physical and behavioural features seen in the fra(X) syndrome.
Molecular studies have shown that 95% of fragile X syndrome cases are caused by the expansion of a CGG triplet in the FMR1 gene with hypermethylation of the adjacent CpG island.
The transcriptional silencing of the human gene, fragile X mental retardation 1 (FMR1), is due to abnormal methylation in response to an expanded 5'-untranslated CGG trinucleotide repeat and accounts for most cases of fragile X syndrome, a frequent inherited form of mental retardation.
We report on the allele distributions in a normal black African population at two microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5' end of the FMR-1 gene, which causes the fragile X syndrome.
These data are consistent with nascent FMRP entering the nucleus to assemble into mRNP particles prior to export back into the cytoplasm and suggests that fragile X syndrome may result from altered translation of transcripts which normally bind to FMRP.
In the present study, we have extended our experiments, and conclude that the Fmr1 knockout mouse is a reliable transgenic model to study the fragile X syndrome.
The pathogenesis of Fragile-X syndrome is a consequence of absence of the FMR1 gene product associated with expansion of the CGG repeat and abnormal methylation of this and a CpG island 250 bp proximal to the CGG repeat located at exon 1 in the FMR1 gene.
The aim is this study is to compare the longitudinal changes in IQ scores of females and males with fragile X syndrome and controls and to assess the impact on IQ of molecular variations of the FMR-1 gene in males.
Females who carry the FMR1 pre and full gene mutation may present with learning, cognitive, and/or emotional difficulties and family members of those diagnosed with fragile X syndrome have ongoing needs and concerns.
Although the phenotype is not completely typical of the FG syndrome and the coincidence of the FMR1 mutation and segregation of the MCA/MR phenotype are highly unlikely, the FMR1 mutation may affect morphogenesis more extensively and differently than the Martin-Bell syndrome does to effect an FG syndromelike phenotype in certain families.