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-se nsitive fragile site on Xq27.3 are commonly associated features. The g ene causing this disorder, designated as FMR1, is X-linked and shows a n unusual inheritance mode. A multistep amplification of the CGG repea ts 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 i ndividuals with the fra-X syndrome, 40 of their relatives (first and s econd degree), and 76 healthy individuals without antecedents of menta l retardation. Southern blot and PCR permitted the assessment of the n umber of CGG repeats and the methylation state of the FMR1 gene for th e normal, premutated, and mutated alleles. The results showed no stati stical differences when compared with those from other populations. No cytogenetic expression of the Xq27.3 fragile site in 50% of the affec ted males and in all the affected and carrier females was observed. Th is finding emphasizes the necessity of a molecular analysis in fra-X c ases and their relatives in order to provide a more adequate genetic c ounseling.