In the era of prevention and early diagnosis, mental retardation (MR) represents one of the most important challenges to modern medicine. Much needs to be done to restrict the number of different forms of this vast category of chronic handicaps for which accurate diagnoses are not yet available. The goal is to reduce the social burden and provide better care for patients and families.

The identification and characterisation of the molecular mechanisms which silence the FMR1 gene and which are responsible, in the majority of cases, for the fragile X syndrome (FRAXA) [1-4], the leading known cause of inherited mental retardation, led to the discovery of an extremely important new class of mutations: “dynamic mutations”. These are highly unstable interspersed repeats, located close to or within genes, which show a strong tendency to expand. This discovery has raised the possibility for direct molecular diagnosis of FRAXA and several other diseases based on the same molecular mechanism, including a different form of MR associated with a fragile site in Xq28, named FRAXE [5].

With these tools, we have started to study the structural characteristics and pattern of transmission of these mutations in a population of mentally retarded individuals mainly coming from north-eastern Italy. The aims of our study were (a) to establish the true incidence of FRAXA and FRAXE full mutations as a cause of mental retardation in our population, and (b) to re-evaluate families in which at least one individual had a cytogenetic fra(X) diagnosis, in order to identify mosaicisms and premutations that could not be identified cytogenetically, and to establish the carrier status of relatives of affected individuals.