POPULATION STUDIES OF THE FRAGILE-X - A MOLECULAR APPROACH

The fragile X mutation can now be recognised by a variety of molecular techniques. We report a pilot screening survey of a population of chi ldren with mental impairment in which we used Southern blotting method s to detect the fragile X mutation, augmented by cytogenetic studies o n children whose phenotype suggested a possible chromosome abnormality . There were 873 children with special educational needs in our survey and 310 fulfilled our criteria for testing. A sample was obtained fro m 254, of whom four were found to have a full fra(X) mutation (DELTAL) and none to have a premutation. The number of CGG repeats in our popu lation of X chromosomes was measured by PCR analysis and the genotype at the closely linked polymorphic locus FRAXAC1 established. The distr ibution of CGG repeat numbers was very similar to that of the control population reported by Fu et al and the distribution of FRAXAC1 allele s almost identical to that of the control population reported by Richa rds et al. Among the non-fragile X chromosomes, we found a very signif icant correlation between the size of the CGG repeat and the FRAXAC1 g enotype. There was a dearth of A and D genotypes in subjects with a sm all number of CGG repeats and an excess of the A genotype in those wit h a large number of CGG repeats. These observations are considered in the light of the reported disequilibrium between the A (and possibly a lso the D) genotype and the fra(X) mutation.