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)

Comparison of the properties of blood platelets and serotonergic synaptosomes suggests that the human platelet can serve as an appropriate model for the transport, metabolism, and release of serotonin (5-HT) by CNS serotonergic neurons. The study of blood 5-HT levels and platelet 5-HT pharmacodynamics in patients with a variety of psychiatric and neurologic disorders has generated interesting leads into possible abnormalities of CNS 5-HT neurons in these patients. This article reviews the experimental evidence, which uses the human platelet model to investigate neurotransmitter-related abnormalities in Down syndrome, mental retardation, infantile autism, hyperactivity syndromes (minimal brain dysfunction), schizophrenia, affective disorders, Duchenne muscular dystrophy, Parkinson disease, Huntington chorea, and migraine headaches.
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PMID:The human platelet. A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders. 14 Jun 32

Recent observations are considered to provide further evidence for an abnormality involving motoneurones in DMD. The dystrophic process appears to take place in two stages of which the first occurs during early embryonic life. This stage is thought to involve faulty inductive actions of the neural tube upon mesoderm and upon itself. The neural consequences vary among individuals and are manifested as mental retardation; EEG abnormalities and losses of functioning motor units. While the first two abnormalities are non-progressive, a further loss of motor units, associated with striking reductions in the numbers of excitable muscle fibers, takes place in trunk and large limb muscles at 9--12 years. The latter process, the cause of which is uncertain, constitutes the second stage of DMD.
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PMID:The neural hypothesis of muscular dystrophy. A review of recent experimental evidence with particular reference to the Duchenne form. 66 46

Cognitive impairment occurs in one-third of patients with Duchenne muscular dystrophy, a lethal X-linked, recessive disease caused by mutations in the dystrophin gene which is expressed in both brain and muscle, the two transcripts having alternative first exons. Previous reports have indicated that the 'brain-type' dystrophin transcript predominates in brain. Using in situ hybridisation with antisense oligonucleotides, expression of four distinct mRNAs in specific brain areas is demonstrated here; the 14 kb muscle-type and brain-type transcripts were found to coexist in cortical and hippocampal neurons and two new transcripts have been identified in dentate gyrus and cerebellar Purkinje neurons, respectively. The latter has a novel first exon which was isolated and sequenced from mouse and human, and which would encode a protein with a different amino-terminus from the known muscle- and brain-type isoforms. Mapping in human located this exon in a large intron between the muscle-type promoter and second exon of the dystrophin gene. This finding of four alternative transcripts regulated by different promoters in brain reveals a new complexity to dystrophin expression that may have important insights for mental retardation mechanisms.
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PMID:Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters. 130 51

Dystrophin, the protein product defective in Duchenne muscular dystrophy (DMD), is present in all types of muscle and in the brain. The function of the protein is unknown and its role in the brain is unclear, although 30% of DMD patients show nonprogressive mental retardation. We have therefore studied the localisation of dystrophin in cultures of normal and DMD human fetal neurons using antibodies raised to different regions of the protein. Dystrophin immunoreactivity was demonstrated in the soma and axon hillock of normal neurons and appeared to be associated with the inner part of the cell membrane, although some intracellular staining was also observed. Positive dystrophin staining was present only in cells with fully developed neuronal features, although not all the neurons were positive. Glial cells were always negative for the antigen. Immunostaining with antibodies to the brain spectrins indicate that the dystrophin antibodies did not crossreact with these proteins. The possibility of cross-reactivity with other proteins is discussed. Studies of cells cultured from a DMD fetus also showed specific dystrophin immunostaining in neurons, although the muscle was generally negative for dystrophin. However, the localisation of dystrophin immunostaining and that of the brain spectrins and neurofilaments appeared abnormal, as did the overall morphology of the cells. This suggests that dystrophin may play a role during brain development and dystrophin deficiency results in abnormal neuronal features. This would be consistent with the nonprogressive nature of the mental retardation observed in DMD patients.
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PMID:Dystrophin immunoreactivity in normal and Duchenne human fetal neurons in culture. 137 3

We report the results of screening for molecular deletions in 164 boys with DMD and BMD and correlation of deletions with clinical features. A deletion was detected in 100 cases (61%) by Southern blot hybridization analysis with cDNA probes. Thirty-eight different deletions and two duplications were identified. All deletions except one (deletion of exons 48-53) found in males with DMD disrupted the translational reading frame of the gene; however, six deletions in boys with BMD were out of frame. The same deletion in different individuals was found to occur with or without mental impairment, and many different deletions were associated with mental retardation. We were able to ascertain a series of boys [from this study and a previous one (Hodgson S V, Hart K, Abbs S, et al. Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy. J Med Genet 1989; 26: 682-693)] without significant mental retardation who had deletions which, when combined, covered the whole region of the gene in which deletions are commonly found, and within which region individual deletions can be associated with mental retardation.
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PMID:Correlation of clinical and deletion data in Duchenne and Becker muscular dystrophy, with special reference to mental ability. 148 53

We studied the central nervous system (CNS) of control mice in comparison with that of mdx mice, immunohistochemically and immunoelectrophoretically, using 5 kinds of polyclonal antibodies against dystrophin (DMDP-II, 60-kDa, 30-kDa, P-20 and DMDP-IV) to determine whether or not and, if so, how dystrophin exists in the central nervous system. A positive dystrophin reaction was seen on the neurons and glial cells in both control and mdx tissue, without any immunohistochemical difference. In control mice, Western blot analysis showed two relatively clear bands corresponding to 400-kDa, with all 4 antibodies used (60-kDa, 30-kDa, P-20 and DMDP-IV), and 280-kDa, with 3 of them, the exception being 30-kDa, and 2 other faint bands corresponding to larger M(r) than 400-kDa, with 3 of them, the exception being P-20, respectively. In the mdx CNS, the 400-kDa band was absent, the other 3 bands being seen. The results suggest that dystrophin really exists in the control CNS, and some dystrophin isoforms or cross-reactive proteins exist on the neurons and glial cells in mdx as well as control mice. The localization of dystrophin in CNS also suggests its physiological function in the conduction system rather than a mechanical one, and a defect of it in CNS is a possible cause of the mental retardation in Duchenne muscular dystrophy.
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PMID:Dystrophin isoforms and/or cross-reactive proteins on neurons and glial cells in control and mdx central nervous systems. 151 55

In an investigation of 15 patients with Duchenne muscular dystrophy, the authors found mental retardation in all cases. In addition, CT scan showed a cortical atrophy after the age of 10 years. This finding suggests that a cerebral degenerative process is present in cases of Duchenne muscular dystrophy.
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PMID:[Mental development in Duchenne muscular dystrophy. Correlation of data of the brain scanner]. 166 37

Thirty per cent of boys with Duchenne muscular dystrophy (DMD) suffer from various degrees of mental retardation. Since dystrophin, the protein absent in muscles of boys with DMD, is produced also in the brain, it was postulated that the deficiency of brain dystrophin might account for the mental retardation found in DMD boys. The mdx mouse, a mouse model of DMD, fails to produce dystrophin in muscle and brain. This prompted us to study the cognitive function of these animals. Learning and memory processes were studied in 10 mdx females and 9 genetically matched controls using the passive avoidance test. Statistically significant differences in the retention of the passive avoidance response was detected between mdx and control mice, indicating an impairment in passive avoidance learning in mdx mice. Our data reinforce the view that brain dystrophin deficiency is correlated with cognitive dysfunction and indicate that mdx mice might be a model for the mental retardation found in DMD boys.
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PMID:Passive avoidance behaviour deficit in the mdx mouse. 182 82

A total of 162 Duchenne (DMD) patients and two girls with a DMD phenotype were analysed for deletions in the central region of the dystrophin gene in order to determine if there was a correlation between mental retardation (MR) and the pattern of deletion. Approximately 43% of the patients studied had deletions with two dystrophin cDNAs, cf23a and cf56a, and among 148 patients who were mentally assessed, 50% were mentally retarded. The average IQ in the group of patients with DNA deletions did not differ significantly from those patients with no detectable deletions. However, six unrelated DMD boys with MR showed an identical pattern of deletion. Our observations in the group of patients who had detected DNA deletions suggest that exon 52 of the dystrophin gene may be functionally significant in the manifestation of MR: 70% (19/27) of patients with a deletion of this exon were mentally retarded, whereas only 38% (15/39) of MR patients had deletions not involving exon 52. This difference was statistically significant.
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PMID:Apparent association of mental retardation and specific patterns of deletions screened with probes cf56a and cf23a in Duchenne muscular dystrophy. 187 22

Dystrophin, the protein product of the Duchenne muscular dystrophy gene, is expressed in brain as well as muscle. The role of dystrophin in the brain is not clear, though one-third of Duchenne muscular dystrophy patients exhibit some degree of mental retardation. We have isolated the genomic region encoding the alternative 5' terminus of dystrophin used in the brain. Primer extension and polymerase chain reaction assays on RNA demonstrate that this region contains an alternative promoter for dystrophin used in the brain. Physical mapping of this region indicates that this brain promoter is located greater than 90 kilobases 5' to the promoter used in muscle and 400 kilobases from exon 2 to which it is spliced. The large physical distance between the promoters, taken together with their known tissue selectivities, suggests that in certain patients a deletion of either dystrophin promoter might give rise to reduced dystrophin expression selective to brain or muscle. We have identified one such individual with specific deletion of the dystrophin muscle promoter, giving rise to Becker muscular dystrophy, and we predict that specific loss of the brain promoter may be one cause of X chromosome-linked mental retardation.
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PMID:Dystrophin is transcribed in brain from a distant upstream promoter. 199 28


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