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

An inherited complete deficiency of hypoxanthine-guanine phosphoribosyltransferase in male children is associated with a severe neurological disorder characterized by chloroform and athetoid movements, hypertonicity, mental retardation, and self-injurious behavior. In the review that follows several possible mechanisms by which the enzyme defect may cause the CNS disorder are discussed. Current evidence suggests that the primary neural deficit in the Lesch-Nyhan syndrome is a deficiency of dopamine in the basal ganglia. It is argued that this neurochemical lesion results from a deficiency of purine nucleotides which impairs arborization of nigrostriatal neurons during perinatal development. Differences in the ontogenetic timing of the neurochemical lesion may be partly responsible for the different neurological symptoms displayed by persons afflicted with the Lesch-Nyhan and Parkinson's syndromes.
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PMID:The biochemical basis of the behavioral disorder in the Lesch-Nyhan syndrome. 392 93

The fragile X(A) or FRAXA syndrome is the most common form of familial mental retardation and is associated with a fragile site at Xq27.3. The gene responsible for the FRAXA syndrome, the FMR1 gene, has been cloned. inactivation of the FMR1 gene is associated with amplification of a trinucle-otide CGG repeat sequence and methylation of an adjacent CpG island. Previous estimates for the prevalence of the FRAXA syndrome have been based on indirect methods of chromosome analysis in institutions and community workshops for the mentally handicapped. We have analyzed the frequency of premutations of the FMR1 gene in 3002 X chromosomes of 1000 male and 1000 female consecutive newborn nonautoclaved blood spots in an anonymous, unlinked survey. The CGG repeat sizes were calculated by measuring the length of products of the PCR reaction based on the molecular size of labeled markers in a denaturing sequencing gel assay. For consistent PCR amplification a DNA microextraction was necessary, including a phenol/chloroform series. In our population, the CGG allele ranged from 9 to 106 repeats: 97% of alleles had fewer than 40 repeats. The most frequent allele was a repeat of 28. Approximately 2.3% of alleles had CGG repeats ranging from 4 to 49 and 0.37% of alleles had repeats ranging from 50 to 59. The frequency of alleles > 60 repeats in the Manitoba male population is approximately 0.13%. The use of nonautoclaved Guthrie blood spots for population screening of FRAXA premutations is not recommended. The necessity of a phenol/chloroform DNA microextraction is tedious and time consuming. The low yield of DNA (250 ng) does not allow for reanalysis by Southern of apparently homozygous females with potentially unstable CGG alleles in the 40-60 repeat range and likely underestimates premutation carrier status.
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PMID:Frequency of FMR1 premutations in a consecutive newborn population by PCR screening of Guthrie blood spots. 859 39