[X chromosome fragility and effects of trimethoprim].

Severe clinical regression was observed in a patient carrier of a fragile X after treatment trimethoprime. This prompted us to examine the effect of this antibiotic in lymphocyte cultures: a dose ranging from 13 mg/l to 53 mg/l increases considerably the frequency of the Xq27 gap in four fragile-X patients; a dose of 13 mg/l allows a normal growth, without appearance of the Xq27 gap, in 19 normal, non-carrier subjects; a dose of 82 mg/l totally inhibits cell division in 10 normal, non carrier subjects. The reversibility of the blockade was demonstrated, either by washing out the trimethoprime before the 50th hour of incubation or by adding 5-formyl-tetrahydrofolate (0.125 mg/l). It is concluded that one of the steps of monocarbon metabolism is inhibited by trimethoprime. This antibiotic, which must be avoided when treating patients carrier of the fragile X can be utilized in vitro for cytogenetic investigations.