Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The fragile site on the X chromosome [fra(X)] associated with mental retardation is not normally seen in lymphocytes cultured in media containing folic acid or lacking methionine. The requirement for methionine has been taken to mean that amino acid metabolism or one-carbon transfer via S-adenosyl-methionine is most important in fra(X) expression. The inhibitory effect of folic acid can be overcome, as we have shown, by the addition of 5'-fluorodeoxyuridine (FUdR) to the culture medium, suggesting that depletion of dTMP available for DNA synthesis is most important in expression. We tested the combined effects of FUdR addition and methionine depletion on the fra(X). We found expression of the fra(X), indicating that methionine per se is not necessary for expression. Our work supports the suggestion that expression of the fra(X) is due to specific limitation of the dTMP pool available for DNA synthesis.
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PMID:The combined effects of FUdR addition and methionine depletion on the X-chromosome fragile site. 621 53

5-Fluoro-2'-deoxyuridine (FUdR) was found to be highly effective in inducing the heritable fragile site on Xq28 associated with mental retardation. Lymphocytes from two affected males manifested the fragile site in 30 to 40% of the mitoses when grown in the presence of FUdR. This observation suggests that depletion of the dTMP pool via thymidylate synthetase inhibition is responsible for the expression of the heritable fragile site on Xq28.
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PMID:5-Fluoro-2'-deoxyuridine induction of the fragile site on Xq28 associated with X linked mental retardation. 646 Jan 4