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)

The treatment of sex offenders with mental retardation is receiving increased attention. Such offenders who are experiencing stress are more likely to use coping strategies effectively if they have a large network of nurturing environmental contacts and are, therefore, less insulated from their environment. In the present study an assessment tool--the ECO-MAP--was used that graphically illustrates the degree of integration of an offender. This instrument has proven to be extremely useful as a clinical aid in the intervention-planning process, the contracting phase of intervention, and in the evaluation of outcomes.
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PMID:Diagrammatic assessment of ecological integration of sex offenders with mental retardation in community residential facilities. 802 99

Prolidase deficiency (PD) is a rare autosomal recessive disorder characterized mainly by skin lesions of the legs and feet, mental retardation, and respiratory infections. Mutations at the PEPD locus, located on chromosome 19, are responsible for this disease. We identified a new PEPD allele in two unrelated Portuguese PD patients by analyses of reverse transcribed PCR-amplified cDNA. We used SSCP analysis of seven overlapping fragments spanning the entire coding region of the gene and detected abnormal SSCP bands in two of them: PD3 (nt 425-743) and PD4 (nt 661-973). Direct sequencing of the mutant cDNA and genomic DNA revealed a new homozygous 3-bp deletion (Y231del) in both cases. Transient expression in PD fibroblasts of wild-type and mutant prolidase cDNA confirmed reduced activity of the construct carrying the 3-bp deletion. The mutation results in a loss of prolidase activity in skin fibroblasts. Intracellular accumulation of Gly-Pro dipeptide in long-term cultured fibroblasts was detected by capillary electrophoresis. The mutation falls in the alpha2 domain of the "pita bread" structure proposed for E. coli and human prolidase by Bazan et al. on the bases of their sequence homology with E. coli methionine aminopeptidase. Taking into account the effects of the described mutations on stability and activity of the enzyme, we propose the identification of three different functional regions.
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PMID:Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship. 1530 82

The doublecortin-like (DCX) domains serve as protein-interaction platforms. DCX tandem domains appear in the product of the X-linked doublecortin (DCX) gene, in retinitis pigmentosa-1 (RP1), as well as in other gene products. Mutations in the human DCX gene are associated with abnormal neuronal migration, epilepsy, and mental retardation; mutations in RP1 are associated with a form of inherited blindness, while DCDC2 has been associated with dyslectic reading disabilities. Motivated by the possible importance of this gene family, a thorough analysis to detect all family members in the mouse was conducted. The DCX-repeat gene superfamily is composed of eleven paralogs, and we cloned the DCX domains from nine different genes. Our study questioned which functions attributed to the DCX domain, are conserved among the different members. Our results suggest that the proteins with the DCX-domain have conserved and unique roles in microtubule regulation and signal transduction. All the tested proteins stimulated microtubule assembly in vitro. Proteins with tandem repeats stabilized the microtubule cytoskeleton in transfected cells, while those with single repeats localized to actin-rich subcellular structures, or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subset interacted with Neurabin 2, and a nonoverlapping group demonstrated actin association. The sub-specialization of some members due to confined intracellular localization, and protein interactions may explain the success of this superfamily.
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PMID:Common and divergent roles for members of the mouse DCX superfamily. 1662 14

Mutations of the MAPT (microtubule-associated protein tau) gene are associated with FTLD (frontotemporal lobar degeneration) with tau pathology. These mutations result in a decreased ability of tau to bind MTs (microtubules), an increased production of tau with four MT-binding repeats or enhanced tau aggregation. In two FTLD patients, we recently described CNVs (copy number variations) affecting the MAPT gene, consisting of a partial deletion and a complete duplication of the gene. The partial deletion resulted in a truncated protein lacking the first MT-binding domain, which had a dramatic decrease in the binding to MTs but acquired the ability to bind MAP (microtubule-associated protein) 1-B. In this case, tauopathy probably resulted from both a loss of normal function and a gain of function by which truncated tau would sequester another MAP. In the other FTLD patient, the complete duplication might result in the overexpression of tau, which in the mouse model induces axonopathy and tau aggregates reminiscent of FTLD-tau pathology. Interestingly, the same rearrangement was also described in several children with mental retardation, autism spectrum disorders and dysmorphic features, as well as in a schizophrenic patient. Finally, complete deletions of the MAPT gene have been associated with mental retardation, hypotonia and facial dysmorphism.
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PMID:Copy number variations involving the microtubule-associated protein tau in human diseases. 2281 14