Molecular characterization of the fragile-X syndrome in the Mexican population

The fragile X (fra-X) syndrome is the most frequent form of inherited mental retardation. Facial dysmorphism, macroorchidism and a folate-sensitive fragile site on Xq27.3 are commonly associated features. The gene causing this disorder, designated as FMR1, is X-linked and shows an unusual inheritance mode. A multistep amplification of the CGG repeats at the 5' end of the FMR1 gene has been recently identified as the cause of the fra-X syndrome. Different numbers of repeats define three gene forms (normal, premutated and mutated), whose ranges show little variation in the populations studied so far. We analyzed 18 Mexican individuals with the fra-X syndrome, 40 of their relatives (first and second degree), and 76 healthy individuals without antecedents of mental retardation. Southern blot and PCR permitted the assessment of the number of CGG repeats and the methylation state of the FMR1 gene for the normal, premutated, and mutated alleles. The results showed no statistical differences when compared with those from other populations. No cytogenetic expression of the Xq27.3 fragile site in 50% of the affected males and in all the affected and carrier females was observed. This finding emphasizes the necessity of a molecular analysis in fra-X cases and their relatives in order to provide a more adequate genetic counseling.