Fragile X expression in normal and mentally retarded subjects: effect of treatment with an antifolic agent

Expression of the fragile site fra(X) (q27.3) in peripheral lymphocytes was evaluated in mentally retarded patients and in normal control individuals before and after administration of the antifolic agent trimethoprim for 7 days. This treatment was effective in converting the status of some individuals from fra(X)-negative to fra(X)-positive. However, the induced level of fra(X) expression was very low and not significantly different in patients and in control subjects and did not increase in those individuals where it was already present before treatment. These data support the contention that fra(X)(q27.3) is a common fragile site and that treatment in vivo with an antifolic agent is not effective in enhancing its degree of expression in vitro. Therefore, such treatment seems to be of no diagnostic value in those cases where the fra(X) syndrome is suspected clinically, but where there is no or very low cytogenetic expression of the fra(X).