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)

Our investigation was concerned with 25 children, 10-13 years old, with an IQ 50-70 ("mild mental retardation," following the ICD). Among these, 14 attended a school for the mentally retarded and 11 one for the learning disabled. A control group was recruited, matched in age, sex and social class. The unipolar 8-channel record of EEG at rest was subjected to blind clinical rating, and a computerized analysis (broad band spectral parameters delta, theta, alpha 1, alpha 2, beta 1, beta 2). A significantly higher frequency of paroxysms was found by the clinical rating. It also allowed the diagnosis of a maturational lag with respect to the items "maturity" and "prominence of alpha rhythm"). Spectral parameters differentiated the two matched groups particularly in bands and leads of developmental relevance (theta, delta, and fronto-central beta in absolute power and theta, delta occipitally and alpha 2, with the exception of frontal leads for relative power).: As is well known, the mentally retarded constitute a heterogeneous group: this could also be verified with respect to EEG activity for the segment of mild mental retardation. A multivariate classification by nonmetric multidimensional scaling yielded a subgroup of 10 children deviant with respect to its overall EEG activity and a group of 15 children within the normal range. This assignment did not overlap with the assignment to the two schools. By computing ratios of broad band power in antero-posterior and symmetric-interhemispheric leads a reduced topographic differentiation was found for the experimental group in their antero-posterior distribution.
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PMID:The EEG of mildly retarded children: developmental, classificatory, and topographic aspects. 618 9

Mutations in the T3-binding domain of the thyroid hormone receptor gene c-erbA beta result in dominant negative proteins and thyroid hormone resistance syndromes. Variable clinical manifestations of resistance to thyroid hormones have been reported, including short stature and neuropsychological abnormalities. The molecular bases for heterogeneity of phenotype among and within kindreds have not been fully elucidated. Recent investigations have considered differential expression of mutant and wild-type beta 1-receptor alleles and the regulation thereof as a mechanism to explain differential sensitivity to thyroid hormones. We used reverse transcription-competitive polymerase chain reaction (PCR) to measure c-erbA beta 1, c-erbA alpha 1, and c-erbA alpha 2 mRNAs in skin fibroblasts cultured from normal subjects, heterozygotes, and a severely affected homozygous mutant of kindred S. The homozygous mutant of kindred S had severe growth and mental retardation. After reverse transcription with primers specific for each of the c-erbA mRNAs, first strand cDNAs were amplified by PCR using subtype-specific amplimers. Primer design allowed simultaneous detection of wild-type and mutant messages in heterozygous fibroblasts and showed an approximately 1:1 ratio of these mRNAs in three patients. Inclusion of competitive standard cDNAs of known concentration in the PCR reactions allowed quantitation of the absolute levels of the beta 1-, alpha 1-, and alpha 2 mRNAs by comparison of products on ethidium bromide-stained agarose gels. These studies showed no effect of the presence of the mutant beta 1-allele, as fibroblast RNA from normal subjects, heterozygotes, and the homozygote gave values of 56-184, 2.8-12, and 23-40 attomol/5 micrograms total RNA for beta 1-, alpha 1-, and alpha 2 mRNAs, respectively. We conclude that these sensitive methods allow the detection of molecular species present at levels as low as 10 molecules/cell, and that this potent dominant negative receptor does not disrupt c-erbA expression at the level of mRNA. The neuropsychological sequelae of the kindred S mutation are not due to relative overexpression of the mutant allele.
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PMID:Competitive polymerase chain reaction quantitation of c-erbA beta 1, c-erbA alpha 1, and c-erbA alpha 2 messenger ribonucleic acid levels in normal, heterozygous, and homozygous fibroblasts of kindred S with thyroid hormone resistance. 840 73

In utero exposure to the anticonvulsant drug phenytoin has been shown to alter normal embryonic development, leading to a pattern of dysmorphogenesis known as the Fetal Hydantoin Syndrome. This embryopathy is characterized by growth retardation, microcephaly, mental deficiency, and craniofacial malformations, although the precise mechanism(s) by which phenytoin alters normal developmental pathways remains unknown. To better understand the molecular events involved in the pathogenesis of phenytoin-induced congenital defects, alterations in gene expression were examined during critical periods of craniofacial development. Pregnant SWV mice were administered phenytoin (60 mg/kg/day) from gestational day 6.5 until they were sacrificed at selected developmental time points. Tissue from the craniofacial region of control and exposed embryos was isolated, and samples were subjected to in situ transcription, antisense RNA amplification, and hybridization on reverse Northern blots to quantitatively assess expression of 36 candidate genes. Chronic phenytoin exposure significantly altered expression of several genes at distinct times during morphogenesis. Results of these studies show that expression of the retinoic acid receptors (RAR) alpha, beta, and gamma were significantly increased by phenytoin exposure. Elevations in gene expression of laminin beta 1, and the growth factors IGF-2, TGF alpha, and TGF beta 1, were also demonstrated in the craniofacial region of phenytoin-exposed embryos. As several of these genes are transcriptionally regulated by retinoic-acid-responsive elements in their promoter regions, phenytoin-induced alterations in expression of the RAR isoforms may have severe downstream consequences in the regulation of events necessary for normal craniofacial development. Such alterations occurring coordinately at critical times during craniofacial development may account for the dysmorphogenesis often associated with phenytoin exposure.
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PMID:Phenytoin-induced alterations in craniofacial gene expression. 998 80

The congenital muscular dystrophies (CMDs) are a heterogeneous group of disorders. Among these, the laminin alpha 2 chain 'merosin' deficient CMD is caused by mutations of the LAMA2 gene on chr 6q2 and Fukuyama CMD is linked to chr 9q31. We report a 7-year-old boy who was born to consanguineous healthy parents. His motor and mental development were slow. Creatine kinase (CK) was elevated (2.100 U/l), and the muscle biopsy was dystrophic. He sat unsupported at 12 months and took his first steps at 3 years of age. At 6 years of age he could walk up to 500 m. He was mentally retarded and spoke single words only. At 1 year, MR imaging of the brain showed abnormal increased periventricular T2-signal, consistent with dysmyelination as well as pontocerebellar hypoplasia and several cerebellar cysts. The pattern of gyration was normal. Follow-up at 4 years showed normalization of the previously abnormal periventricular T2-signal. Immunohistochemical analysis of the skeletal muscle showed normal expression of laminin alpha 2 for a C-terminal antibody and antibodies to the 300 and 150 kDa fragments, as well as of laminins alpha 5, beta 1, beta 2 and gamma 1. The boy has two healthy younger brothers. Linkage analysis excluded the candidate loci on chromosomes 6q2 and 9q31. As such, the patient's data are suggestive of a new form of laminin alpha 2 positive CMD characterized by transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation.
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PMID:Merosin-positive congenital muscular dystrophy with transient brain dysmyelination, pontocerebellar hypoplasia and mental retardation. 1022 Aug 64