Frequency and stability of the fragile X premutation

Although considered the most common heritable cause of neurodevelopmental disability, precise prevalence figures for the FMR1 mutation in the general population are lacking. Since no fragile X premutation alleles have yet been observed to originate from FMR1 alleles within the normal size range, there is also little information available about the origin of the fragile X premutation and mechanisms leading to instability of the FMR1 trinucleotide repeat region. In this study, 977 genetically unrelated individuals from families unselected for mental retardation or fragile X were analyzed with Southern blot analysis for the presence of FMR1 mutations. A subgroup of subjects with evidence of a large CGG repeat number, and any available relatives, were further studied with PCR to investigate the stability of the trinucleotide repeat segment of FMR1