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[X chromosome fragility and effects of trimethoprim]
Abstract:
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.
Insights
Trimethoprim antibiotic treatment caused severe regression in a fragile X patient. This drug increases the Xq27 gap in fragile X carriers and inhibits cell division in normal subjects.
Area of Science:
- Genetics
- Pharmacology
- Cell Biology
Background:
- Fragile X syndrome is a genetic disorder.
- Trimethoprim is an antibiotic commonly used to treat bacterial infections.
Observation:
- A patient with fragile X syndrome experienced severe clinical regression after trimethoprim treatment.
- In vitro studies showed trimethoprim increased the Xq27 gap frequency in fragile X patient lymphocytes.
- Trimethoprim inhibited cell division in normal lymphocytes at higher concentrations.
Findings:
- Trimethoprim significantly increases the Xq27 gap in fragile X carriers.
- The antibiotic's effects on cell division are reversible with folate.
- Trimethoprim appears to inhibit a step in monocarbon metabolism.
Implications:
- Trimethoprim should be avoided in fragile X patients.
- Trimethoprim may have potential in vitro applications for cytogenetic analysis of fragile X.
- Understanding trimethoprim's metabolic inhibition offers insights into folate pathway disorders.