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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultrastructural studies of cerebral biopsy specimens from patients with various forms of psychomotor retardation and dementia have disclosed pathologic changes in axons and presynaptic or postsynaptic processes. The clinical disorders with lesions in axons and presynaptic terminals are reviewed. Three basic abnormalities have been detected: proliferation of tubulovesicular structures which probably originate from the smooth endoplasmic reticulum, "abnormal" mitochondria, and proliferation of 80 to 100 A filaments. Understanding of the pathogenesis of human disorders associated with axonic or "synaptic" lesions will probably depend on progress in areas of basic biomedical research concerned with the synthesis and turnover of biological membranes and the packaging and secretion of neurotransmitters, elucidation of mechanisms of cytoplasmic streaming and axoplasmic flow, and biophysical and biochemical characteristics and functions of "fibrous" proteins (neurotubules, neurofilaments, pathologic fibrous proteins). In several cases of mental retardation of unknown etiology, abnormal dendritic spines of cortical neurons have been observed with the use of the Golgi method. These dendritic (postsynaptic) disorders have been attributed to defective development ("dysgenesis"). The knowledge provided by ultrastructural analysis of brain tissue from the human disorders of mental retardation or dementia is "still formless, incomplete, lacking the essential threads of connection," and only future developments in lacking neurobiology will make possible the dissection of the primary phenomena from the secretory and probably irrelevant findings.
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PMID:Pathologic axons and synapses in human neuropsychiatric disorders. 17 Jan 88

A case of a human male infertility with chromosomal aberration is reported. The patient showed neither mental retardation nor physical abnormalities except that the testes were somewhat small and soft. Plasma follicle stimulating hormone and luteinizing hormone were 49.0 and 19.0 mIU/ml. Plasma testosterone was 2.6 ng/ml. Karyotype was considered to be 46 XY q-, long arms of the Y chromosome being deleted. Histological features of the testis were peculiar. Seminiferous tubules were small and devoid of spermatogenic cells, consisting only of Sertoli cells. Peritubular boundary layer of the tubules showed a marked increase in width due to the increase of collagen fibers. The base of some Sertoli cells was seen to protrude into the thickened peritubular boundary layer or, though rare, into the interstitial space. Unusual cells which had a round vesicular nucleus and abundant, dense cytoplasms also occurred in the boundary layer of most tubules. These cells were identified as Leydig cells because of an extensively developed smooth endoplasmic reticulum in their cytoplasm, although they lacked Reinke's crystals. These ectopic Leydig cells sometimes lay in direct contact with Sertoli cells in the seminiferous tubule.
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PMID:Ectopic Leydig cells in a seminiferous tubules of an infertile human male with a chromosomal aberration. 56 84

Thyroid hormone exerts a powerful influence on CNS growth and maturation. Hypothyroidism early in life has long been known to cause disturbances in innate behavior, motor performance, severe and frequently irreversible mental retardation. In this deficiency, depressed caudate neurogenesis, cell migration and neuropil development during the rapid period of CNS growth may contribute to the clinical picture of perceptual handicaps often seen in cretins. Light microscopic and Golgi studies of the developing caudate nucleus in thyroid deficiency have been carried out to help attain insights into the mechanisms whereby the extrapyramidal system regulates motor function. The ultrastructural study of caudate nuclear cytogenesis and synaptogenesis in normal and hypothyroid states provides more detailed information for further analysis of the problem. Hypothyroidism was induced from birth by adding prophylthiouracil to the food and drinking water of lactating dams. Linear development of the caudate nucleus of both normal and hypothyroid rats at ages 8, 14, 20, 30 and 42 days was studied by electron microscopy. Thyroid glands were examined by light microscopy to assess the normal and deficient states. Immature cells, primitive processes and synapses were the characteristic features of the 8-day-old normal caudate nucleus. Distinctively wide cisternae of the rough endoplasmic reticulum, loosley packed Golgi apparatus and chromatin clumps throughout the nuclei of the neurons were significant early morphologic variations. The dramatic cytoarchitectural maturation in the 14- and 20-day normal caudate neuropil points to the rapidity of developmental rate. After the growth spurt of the first three weeks a maturational plateau occurs which is characterized by well-formed neuronal cytoplasmic organelles, myelinated and non-myelinated axons, axon terminals, dendrites and their spines, and synapses. Thyroid deficiency causes a marked maturational delay of approximately 7 days in caudate neuronal proliferation, the elaboration of neuronal networks and the attainment of mature synaptic contents and membranes. This delay is evidenced by comparison of the structural similarities between 8-day-old normal and 14-day-old deficient rats; and additional comparisons between the 14-day-old normal and 20-day-old hypothyroid rats. A rapid "catch up" process in fine structural morphogenesis takes place in the period between days 14 and 30 in the deficient animals. Repression of thyroid function does not entirely prevent development of the caudate nucleus but allows a fairly extensive, though critically incomplete degree of maturation. This imperfection is manifested by a decrease in the number of synaptic contacts that persists even after the rapid "catch up" phenomenon of caudate synaptogenesis.
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PMID:An electron microscopic study of the developing caudate nucleus in euthyroid and hypothyroid states. 86 26

The fragile X syndrome, one of the most common forms of inherited mental retardation, is caused by an expansion of a polymorphic CGG repeat upstream the coding region of the FMR1 gene. These expansions are associated with hypermethylation of the FMR1 gene, which results in the absence of the gene product, the FMR1 protein (FMRP). The physiological function of FMRP remains to be determined. We studied the ultrastructural localization of FMRP at the electron microscopical level using the immunogold technique. FMRP is associated with ribosomes attached to the endoplasmic reticulum and with ribosomes free in the cytoplasm. In addition, FMRP is found in the nucleus where the protein is associated with the granular component of the nucleolus. The cellular function of FMRP is hypothesized in relation to its subcellular distribution.
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PMID:Association of FMRP with ribosomal precursor particles in the nucleolus. 876 90

Fragile X syndrome, a leading cause of inherited mental retardation, is attributable to the unstable expansion of a CGG-repeat within the FMR1 gene that results in the absence of the encoded protein. The fragile X mental retardation protein (FMRP) is a ribosome-associated RNA-binding protein of uncertain function that contains nuclear localization and export signals. We show here detailed cellular localization studies using both biochemical and immunocytochemical approaches. FMRP was highly expressed in neurons but not glia throughout the rat brain, as detected by light microscopy. Although certain structures, such as hippocampus, revealed a strong signal, the regional variation in staining intensity appeared to be related to neuron size and density. In human cell lines and mouse brain, FMRP co-fractionated primarily with polysomes and rough endoplasmic reticulum. Ultrastructural studies in rat brain revealed high levels of FMRP immunoreactivity in neuronal perikarya, where it is concentrated in regions rich in ribosomes, particularly near or between rough endoplasmic reticulum cisternae. Immunogold studies also provided evidence of nucleocytoplasmic shuttling of FMRP, which was localized in neuronal nucleoplasm and within nuclear pores. Moreover, labeling was observed in large- and small-caliber dendrites, in dendritic branch points, at the origins of spine necks, and in spine heads, all known locations of neuronal polysomes. Dendritic localization, which was confirmed by co-fractionation of FMRP with synaptosomal ribosomes, suggests a possible role of FMRP in the translation of proteins involved in dendritic structure or function and relevant for the mental retardation occurring in fragile X syndrome.
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PMID:Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes. 903 Jun 14

Dyggve-Melchior-Clausen syndrome without mental retardation (Smith-McCort dysplasia) (SM) has clinical and radiographic findings similar to those of Dyggve-Melchior-Clausen syndrome (DMC) except for mental retardation. Iliac crest biopsies from two patients with SM were examined. The lace-like appearance of the iliac crests, which is a characteristic radiological sign of SM and DMC, was caused by bone tissue deposited in a wavy pattern at the osteochondral junction. The growth plate showed abnormal enchondral ossification with no columnarization of chondrocytes. Electron microscopy demonstrated chondrocytes with dilated cisternae of rough endoplasmic reticulum containing fine granular or amorphous material, similar to those reported in cases of DMC. Thus, SM has pathologic changes in common with DMC as a rough endoplasmic reticulum storage disorder, even though the mental condition is different.
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PMID:Dyggve-Melchior-Clausen syndrome without mental retardation (Smith-McCort dysplasia): morphological findings in the growth plate of the iliac crest. 929 67

Myotonic dystrophy protein kinase (DMPK) is the protein product of the genetic locus associated with myotonic dystrophy, in which alterations of muscle excitability, cardiac conduction defects, mental retardation, and cognitive deficiencies are inherited as an autosomal dominant trait. DMPK belongs to a novel protein serine/threonine kinase family, but its regulation and physiological functions have not been specified. In a first step toward understanding the functions of DMPK in the central nervous system, we have characterized its localization and developmental pattern of expression in rat brain and spinal cord by using a monospecific rabbit antiserum produced against bacterially expressed DMPK. Expression of DMPK begins after birth and increases gradually to peak at postnatal day 21 with antibody labeling of neuronal cell types in many regions. After postnatal day 21 and proceeding to the adult, the pattern of expression becomes more restricted, with localization to certain regions or cell groups in the central nervous system. Electron microscopy reveals localization within adult spinal motor neurons to the endoplasmic reticulum and dendritic microtubules. The adult localizations suggest that DMPK may function in membrane trafficking and secretion within neurons associated with cognition, memory, and motor control.
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PMID:Developmental changes in expression of myotonic dystrophy protein kinase in the rat central nervous system. 957 95

Darier's disease (DD) is a rare, dominantly inherited disorder that affects the skin producing a variety of types of lesion. Close examination of lesional DD skin shows the presence of abnormal keratinization (epidermal differentiation) and acantholysis (loss of cohesion) of keratinocytes. A number of clinical studies have described the co-occurrence of various neurological and psychiatric symptoms with DD, including mood disorders, epilepsy, mental retardation and a slowly progressive encephalopathy. A single locus for DD has been mapped to chromosome 12q23-q24.1, and a variety of missense, nonsense, frameshift and splicing mutations in the ATP2A2 gene have been described recently in families with DD. This gene encodes the sarcoplasmic/endoplasmic reticulum calcium-pumping ATPase SERCA2, which has a central role in intra-cellular calcium signalling. In this study, we performed mutation analysis on ATP2A2 in 19 unrelated DD patients, of whom 10 had neuropsychiatric phenotypes. We identified and verified 17 novel mutations predicting conservative and non-conservative amino acid changes, potential premature translation terminations and potential altered splicing. Our findings confirm that mutations in ATP2A2 are associated with DD. In neuropsychiatric cases, there was a non-random clustering of mutations in the 3' end of the gene ( P = 0.01), and a predominance of the missense type (70% versus 38% in DD patients). This supports the hypothesis that the DD gene has pleiotropic effects in brain and that mutations in SERCA2 are implicated in the pathogenesis of neuropsychiatric disorders.
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PMID:ATP2A2 mutations in Darier's disease and their relationship to neuropsychiatric phenotypes. 1044 25

Fragile X syndrome, a common form of inherited mental retardation, is mainly caused by massive expansion of CGG triplet repeats located in the 5'-untranslated region of the fragile X mental retardation-1 ( FMR1 ) gene. In patients with fragile X syndrome, the expanded CGG triplet repeats are hypermethylated and the expression of the FMR1 gene is repressed, which leads to the absence of FMR1 protein (FMRP) and subsequent mental retardation. FMRP is an RNA-binding protein that shuttles between the nucleus and cytoplasm. This protein has been implicated in protein translation as it is found associated with polyribosomes and the rough endoplasmic reticulum. We discuss here the recent progress made towards understanding the molecular mechanism of CGG repeat expansion and physiological function(s) of FMRP. These studies will not only help to illuminate the molecular basis of the general class of human diseases with trinucleotide repeat expansion but also provide an avenue to understand aspects of human cognition and intelligence.
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PMID:Understanding the molecular basis of fragile X syndrome. 1076 13

Progressive epilepsy with mental retardation (EPMR) is a new member of the neuronal ceroid lipofuscinoses (NCLs). The CLN8 gene underlying EPMR was recently identified. It encodes a novel 286 amino acid transmembrane protein that contains an endoplasmic reticulum (ER)-retrieval signal (KKRP) in its C-terminus. A homozygous mutation in the orthologous mouse gene (Cln8) underlies the phenotype of a naturally occurring NCL model, the motor neuron degeneration mouse (mnd). To characterize the product of the CLN8 gene and to determine its intracellular localization, we expressed CLN8 cDNA in BHK, HeLa and CHO cell lines. In western blotting and pulse-chase analyses an approximately 33 kDa protein that does not undergo proteolytic processing steps was detected. Using CLN8 and cell organelle specific antibodies with confocal immunofluorescence microscopy the CLN8 protein was shown to localize in the ER. Partial localization to the ER-Golgi intermediate compartment (ERGIC) was also observed. The ER-ERGIC localization was not altered in the CLN8 protein representing the EPMR mutation. However, mnd mutant protein was only found in the ER. Mutations in the ER retrieval signal KKRP resulted in localization of CLN8 to the Golgi apparatus. Taken together, these data strongly suggest that CLN8 is an ER resident protein that recycles between ER and ERGIC.
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PMID:The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum. 1086 Dec 96


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