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)

Phenylalanine hydroxylase (PheOH) catalyzes the conversion of L-phenylalanine to L-tyrosine, the rate-limiting step in the oxidative degradation of phenylalanine. Mutations in the human PheOH gene cause phenylketonuria, a common autosomal recessive metabolic disorder that in untreated patients often results in varying degrees of mental retardation. We have determined the crystal structure of human PheOH (residues 118-452). The enzyme crystallizes as a tetramer with each monomer consisting of a catalytic and a tetramerization domain. The tetramerization domain is characterized by the presence of a domain swapping arm that interacts with the other monomers forming an antiparallel coiled-coil. The structure is the first report of a tetrameric PheOH and displays an overall architecture similar to that of the functionally related tyrosine hydroxylase. In contrast to the tyrosine hydroxylase tetramer structure, a very pronounced asymmetry is observed in the phenylalanine hydroxylase, caused by the occurrence of two alternate conformations in the hinge region that leads to the coiled-coil helix. Examination of the mutations causing PKU shows that some of the most frequent mutations are located at the interface of the catalytic and tetramerization domains. Their effects on the structural and cellular stability of the enzyme are discussed.
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PMID:Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. 964 59

This summary provides an overview of the assessment and treatment recommendations contained in the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults With Mental Retardation and Comorbid Mental Disorders. The parameters were written to aid clinicians in the assessment and treatment of children, adolescents, and adults with symptoms of mental retardation (MR) and comorbid mental disorders. MR is a heterogeneous condition defined by significantly subaverage intellectual and adaptive functioning and onset before age 18 years. With an approach underscored by principles of normalization and the availability of appropriate education and habilitation, persons with MR generally live, are educated, and work in the community. Mental disorders occur more commonly in persons with MR than in the general population. However, the disorders themselves are essentially the same. Clinical presentations can be modified by poor language skills and by life circumstances, so a diagnosis might hinge more heavily on observable behavioral symptoms. The diagnostic assessment considers and synthesizes the biological, psychological, and psychosocial context of mental disorders. Comprehensive treatment integrating various approaches, including family counseling, pharmacological, educational, habilitative, and milieu interventions is the rule.
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PMID:Summary of the Practice Parameters for the Assessment and Treatment of Children, Adolescents, and Adults with Mental Retardation and Comorbid Mental Disorders. American Academy of Child and Adolescent Psychiatry. 1059 63

DCX mutations cause mental retardation in male subjects with lissencephalypachygyria and in female subjects with subcortical band heterotopia (SBH). We observed four families in which carrier women had normal brain magnetic resonance imaging (MRI) and mild mental retardation, with or without epilepsy. Affected male subjects had SBH or pachygyria-SBH. In two families, the phenotype was mild in both genders. In the first family, we found a tyr138his mutation that is predicted to result in abnormal folding in the small hinge region. In the second family, we found an arg178cys mutation at the initial portion of R2, in the putative beta-sheet structure. Carrier female subjects with normal MRI showed no somatic mosaicism or altered X-inactivation in lymphocytes, suggesting a correlation between mild mutations and phenotypes. In the two other families, with severely affected boys, we found arg76ser and arg56gly mutations within the R1 region that are predicted to affect DCX folding, severely modifying its activity. Both carrier mothers showed skewed X-inactivation, possibly explaining their mild phenotypes. Missense DCX mutations may manifest as non-syndromic mental retardation with cryptogenic epilepsy in female subjects and SBH in boys. Mutation analysis in mothers of affected children is mandatory, even when brain MRI is normal.
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PMID:Nonsyndromic mental retardation and cryptogenic epilepsy in women with doublecortin gene mutations. 1283 18