AGG interspersion analysis of the FMR1 CGG repeats in mental retardation of unspecific cause

Objectives To study the AGG interspersion pattern in mentally retarded patients of unspecified cause. Methods FMR1 CGG substructure in 104 normal and 232 mentally retarded (MR) males was determined by CGG repeat and AGG interspersion analyses. Genomic DNA of the study subjects was obtained for PCR and Southern hybridization analyses. Results All study subjects had less than 53 CGG repeats and none had fragile X syndrome of mental retardation. There was a significant difference (P < 0.006) in the AGG interspersion pattern. MR males had (1) more variable internal substructures, (2) proportionally less 2 and 3 AGG but more 0 and 1 AGG, less (CGG)9AGG(CGG)9AGG(CGG)9 but more (CGG)9AGG(CGG)19 alleles and (3) a longer pure 3′ CGG repeat. Conclusions Our results suggest that the MR alleles have a lesser number of interspersed AGG and a longer pure 3′ CGG repeat than the normal population. They are thus more prone to instability and expansion to long repeat lengths as in the fragile X syndrome of mental retardation.