Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoamine oxidase (MAO) exists as two isoenzymes and plays a central role in the metabolism of monoamine neurotransmitters. In this study we compared the neurochemical phenotypes of previously described subjects with genetically determined selective lack of MAO-A or a lack of both MAO-A and MAO-B with those of two subjects with a previously described X chromosome microdeletion in whom we now demonstrate selective MAO-B deficiency. Mapping of the distal deletion breakpoint demonstrates its location in intron 5 of the MAO-B gene, with the deletion extending proximally into the Norrie disease gene. In contrast to the borderline mental retardation and abnormal behavioral phenotype in subjects with selective MAO-A deficiency and the severe mental retardation in patients with combined MAO-A/MAO-B deficiency and Norrie disease, the MAO-B-deficient subjects exhibit neither abnormal behavior nor mental retardation. Distinct neurochemical profiles characterize the three groups of MAO-deficient patients. In MAO-A-deficient subjects, there is a marked decrease in deaminated catecholamine metabolites and a concomitant marked elevation of O-methylated amine metabolites. These neurochemical changes are only slightly exaggerated in patients with combined lack of MAO-A and MAO-B. In contrast, the only biochemical abnormalities detected in subjects with the MAO-B gene deletion are a complete absence of platelet MAO-B activity and an increased urinary excretion of phenylethylamine. The differences in neurochemical profiles indicate that, under normal conditions, MAO-A is considerably more important than MAO-B in the metabolism of biogenic amines, a factor likely to contribute to the different clinical phenotypes.
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PMID:Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes. 861 23

During the 1960's, reports suggesting the existence of multiple forms of monoamine oxidase (MAO) appeared with increasing frequency. In July 1968, two reports appeared in the same issue of Biochemical Pharmacology that established the existence of MAO-A and MAO-B. This terminology was unanimously accepted at an international meeting on MAO in 1971. MAO-A preferentially deaminates serotonin (5HT) and is selectively inhibited by harmine and clorgyline, while MAO-B preferentially deaminates phenethylamine and benzylamine, and is selectively inhibited by (-)deprenyl as well as low concentrations of pargyline. It was later found that MAO-A and MAO-B are encoded by separate genes. The two genes have identical exon-intron organizations, but differ with respect to their promoters. In humans both genes are located very close together on the short arm of the X chromosome (Xp21-p11). In mice, the MAO-A gene is also located on the X chromosome, but the chromosomal locations of the MAO-A and -B genes for other species appear to be unknown at present. Some degree of polymorphism seem to exist in both genes. Both forms probably occur naturally as homodimers in the mitochondrial outer membrane, raising the possibility of 3 variants of both MAO-A and -B in human females that are heterozygous for alleles at each locus. Highly specific antibodies for MAO-A and -B, respectively, have been produced, and immunohistochemical studies show that the two forms are differentially expressed in different cell types. In rat and primate brain MAO-A is restricted to catecholamine neurons, while MAO-B is largely restricted to serotonin neurons and astrocytes. Congenital lack of MAO-A is associated with mental retardation, impulsive aggressive behavior and other behavioral/neurological disorders. These results support the conclusion that both MAO-A and -B play predominantly protective roles in the organism.
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PMID:[Discovery of monoamine oxidase forms A and B]. 950 61

Brunner et al. [1993: Am J Hum Genet 52: 1032-1039; 1993: Science 262:578-580] described males with an MAO-A deficiency state resulting from a premature stop codon in the coding region of the MAOA gene. This deficiency state was associated with abnormal levels of amines and amine metabolites in urine and plasma of affected males, as well as low normal intelligence and apparent difficulty in impulse control, including inappropriate sexual behavior. In the present study, disruption of the MAOA gene was evaluated in males with mental retardation with and without a history of sexually deviant behavior, as well as normal controls, healthy males, and patients with other diseases (Parkinson disease, Lesch-Nyhan syndrome). When available, plasma samples were evaluated first for levels of 3-methoxy, 4-hydroxyphenolglycol (MHPG), a metabolite of norepinephrine which serves as the most sensitive index of MAO-A activity in humans. Blood DNA from individuals with abnormally low MHPG, and from other individuals for whom metabolite levels were not available, were screened for nucleotide variations in the coding region of the MAOA gene by single-strand conformational polymorphism (SSCP) analysis across all 15 exons and splice junctions, and by sequencing, when indicated by either altered metabolites or SSCP shifts. No evidence for mutations disrupting the MAOA gene was found in 398 samples from the target populations, including institutionalized mentally retarded males (N = 352) and males participating in a sexual disorders clinic (N = 46), as well as control groups (N = 75). These studies indicate that MAOA deficiency states are not common in humans.
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PMID:Screen for MAOA mutations in target human groups. 1005 Sep 62