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)

Angelman syndrome (AS) is a neurological disorder with a heterogeneous genetic aetiology. It most frequently results from a de novo interstitial deletion in the 15q11-q13 region, but in a few cases it is caused by paternal uniparental disomy (UPD) or an imprinting mutation. The remaining 20 to 30% of AS patients exhibit biparental inheritance and a normal pattern of allelic methylation in the 15q11-q13 region. In this latter group, mutations in the UBE3A gene have recently been shown to be a cause of AS. Here we describe the phenotypic expression in 14 AS cases involving eight UBE3A mutations. These comprise 11 familial cases from five families and three sporadic cases. Subtle differences from the typical phenotype of AS were found. Consistent manifestations were psychomotor delay, a happy disposition, a hyperexcitable personality, EEG abnormalities, and mental retardation with severe speech impairment. The other main manifestations of AS, ataxia, epilepsy, and microcephaly, were either milder or absent in various combinations among the patients. In addition, myoclonus of cortical origin was frequently observed with severe fits inducing myoclonic seizures. The majority of the patients were overweight. This study showed that ataxia, myoclonus, EEG abnormalities, speech impairment, characteristic behavioural phenotype, and abnormal head circumference are attributable to a deficiency in the maternally inherited UBE3A allele. Furthermore, analysis of mutation transmission showed an unexpectedly high rate of somatic mosaicism in normal carriers. These data have important consequences for genetic counselling.
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PMID:Angelman syndrome resulting from UBE3A mutations in 14 patients from eight families: clinical manifestations and genetic counselling. 1042 18

The structure of a Nova protein K homology (KH) domain recognizing single-stranded RNA has been determined at 2.4 A resolution. Mammalian Nova antigens (1 and 2) constitute an important family of regulators of RNA metabolism in neurons, first identified using sera from cancer patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia (POMA). The structure of the third KH domain (KH3) of Nova-2 bound to a stem loop RNA resembles a molecular vise, with 5'-Ura-Cyt-Ade-Cyt-3' pinioned between an invariant Gly-X-X-Gly motif and the variable loop. Tetranucleotide recognition is supported by an aliphatic alpha helix/beta sheet RNA-binding platform, which mimics 5'-Ura-Gua-3' by making Watson-Crick-like hydrogen bonds with 5'-Cyt-Ade-3'. Sequence conservation suggests that fragile X mental retardation results from perturbation of RNA binding by the FMR1 protein.
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PMID:Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. 1067 14

Myoclonic jerks occur in a number of different syndromes. There is many classifications of myoclonus. It is preferred the Fejerman classification, slightly modified that present the following five groups: 1. Myoclonus without encephalopathy and without epilepsy, which includes physiological myoclonus; 2. Encephalopathies with non epileptic myoclonus, which includes Kinsbourne syndrome and certain types of hyperekplexia which pose differential diagnosis problems with reflex myoclonic epilepsy; 3. Progressive encephalopathies with myoclonic seizures which includes typical and atypical progressive myoclonus epilepsies; 4. Epilepsies and epileptic encephalopathies with myoclonic seizures, which includes severe epilepsies which leads to mental retardation, as Otahara syndrome, West syndrome and Lennox-Gastaut syndrome, and other epilepsies which present sometimes myoclonic seizures, as Landau-Kleffner syndrome, 5. Comprises true myoclonic epilepsies, differentiating syndromes recognized as idiopathic, -benign myoclonic epilepsy of infancy, reflex form of benign myoclonic epilepsy in infancy, eyelid myoclonic with absences, perioral myoclonic with absences and juvenile myoclonic epilepsy-, cryptogenic-severe myoclonic epilepsy of infancy, myoclonic-astatic epilepsy and epilepsy with myoclonic absences-, and symptomatic as the generalized myoclonus in children with static encephalopathies. The epileptic syndromes of the last group are described. Despite this classification, apparently clear, there is still a great deal of confusion and in clinical practice, many cases are difficult to classify.
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PMID:[Myoclonus and myoclonic epilepsies in childhood]. 1071 97

Sialidosis is an autosomal recessive disease caused by the genetic deficiency of lysosomal sialidase, which catalyzes the hydrolysis of sialoglycoconjugates. The disease is associated with progressive impaired vision, macular cherry-red spots and myoclonus (sialidosis type I) or with skeletal dysplasia, Hurler-like phenotype, dysostosis multiplex, mental retardation and hepatosplenomegaly (sialidosis type II). We have analyzed the genomic DNA from nine sialidosis patients of multiple ethnic origin in order to find mutations responsible for the enzyme deficiency. The activity of the identified variants was studied by transgenic expression. One patient had a frameshift mutation (G623delG deletion), which introduced a stop codon, truncating 113 amino acids. All others had missense mutations: G679G-->A (Gly227Arg), C893C-->T (Ala298Val), G203G-->T (Gly68Val), A544A-->G (Ser182Gly) C808C-->T (Leu270Phe) and G982G-->A (Gly328Ser). We have modeled the three-dimensional structure of sialidase based on the atomic coordinates of the homologous bacterial sialidases, located the positions of mutations and estimated their potential effect. This analysis showed that five mutations are clustered in one region on the surface of the sialidase molecule. These mutations dramatically reduce the enzyme activity and cause a rapid intralysosomal degradation of the expressed protein. We hypothesize that this region may be involved in the interface of sialidase binding with lysosomal cathepsin A and/or beta-galactosidase in their high-molecular-weight complex required for the expression of sialidase activity in the lysosome.
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PMID:Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. 1076 32

The possible associations of myoclonic phenomenae, progressive or non-progressive encephalopathies and epileptic features are reviewed, with special emphasis on pediatric age. This leads to recognize the following five groups of conditions: (1) Myoclonus without encephalopathy and without epilepsy; (2) Encephalopathies with non-epileptic myoclonus; (3) Progressive encephalopathies presenting myoclonus seizures of epileptic syndromes (Progressive myoclonus epilepsies); (4) Epileptic encephalopathies with myoclonic seizures; (5) Myoclonic epilepsies. Within the first group, which also includes physiologic myoclonus, a more thorough description of "Benign sleep myoclonus of newborn" and "Benign myoclonus of early infancy" is given. Characteristics of group 2 are "Kinsbourne Syndrome" and certain types of "Hyperekplexia" which pose interesting differential diagnosis with stimulus-sensitive epilepsies. In group 3, the concept of progressive encephalopathies is stressed. The fourth group refers to severe epilepsies, mainly on infancy and childhood, which lead to mental retardation irrespective of their aetiology. Group 5 comprises the true myoclonic epilepsies, differentiating syndromes recognized as idiopathic--such as "Benign myoclonic epilepsy of infancy" and "Juvenile myoclonic epilepsy"--from those which are cryptogenic and carry a more cautious prognosis--as "Cryptogenic myoclonic and myoclonoastatic epilepsies" and "Severe myoclonic epilepsy of infancy". Other epileptic syndromes not usually considered as myoclonic epilepsies, but presenting sometimes as myoclonic seizures, are finally referred.
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PMID:Myoclonus and epilepsies. 1077 93

We reported an autopsy case of neuronal ceroid-lipofuscinosis (NCL3) with dilatated cardiomyopathy. A 29-year-old male patient first noticed night-blindness at the age of four years. He was pointed out retinitis pigmentosa at the age of six years and developed ataxia, mental retardation, epilepsy and myoclonus, thereafter. T1 weighted MRI showed diffuse atrophy of the cerebellum, brainstem, and cerebrum, and dilatation of the ventricular system and T2-weighted MRI showed mild high signal intensity in the white matter around the trigones of the lateral ventricles. Autopsy findings showed an abundant accumulation of ceroid-lipofuscin-like lipopigments in most neurons in the central nervous system, and curvilinear bodies and lipofuscin like granules were confirmed by electron microscopy. The heart muscle showed an increase in the accumulation of ceroid-lipofuscin-like lipopigments, severe fibrosis and fatty infiltration in the myocardium. The peculiar point of this case is NCL3 with dilated cardiomyopathy.
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PMID:[An autopsy case of juvenile neuronal ceroid-lipofuscinosis with dilated cardiomyopathy]. 1096 52

Pathology and associated clinical symptoms of hereditary dentatorubral-pallidoluysian atrophy (H-DRPLA) which was established as a new inherited neurodegenerative disease in 1982 are described. Obligatory lesions in the central nervous system combine with degeneration of the dentatorubral and pallidoluysian pathway, and occasional degenerative lesions are found in the cerebral white matter, putamen, Goll's nucleus of the medulla oblongata, and lateral corticospinal and Goll's tract of the spinal cord. The main clinical symptoms are myoclonus, epilepsy, dementia or mental retardation, cerebellar ataxia and choreoathetosis. Furthermore, newly developing aspects in the pathology of H-DRPLA following the discovery of the gene locus of H-DRPLA in 1994 are briefly described.
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PMID:Hereditary dentatorubral-pallidoluysian atrophy. 1103 86

For the treatment of intractable generalized epilepsies, two-staged total callosotomy was performed in five patients. In all patients, preceded anterior callosotomy failed to obtain satisfactory seizure control. All patients showed mental retardation with various degrees. Mean age at the first operation was 10.2 years and 4 patients were operated in their childhood. All patients showed various types of seizures; drop attack (DA) in 3 patients, tonic seizure (TS) in 2, myoclonus (MY) in 2, complex partial seizure (CPS) in 2, atypical absence (AA) in 1, and head drop (HD) in 2. After anterior callosotomy, complete cessation of CPS and 50-80% reduction of DA was obtained in one, respectively. However, only less than 50% reduction of seizures was obtained in other types of seizures. Two years after anterior callosotomy, posterior portion of the corpus callosum was divided. After staged total callosotomy, complete cessation of DA was obtained in all patients and 80-100% reduction of AA was obtained in one patient. One adult patient showed the disconnection syndrome which did not affect activities of his daily life. Our study revealed the efficacy of posterior callosotomy in DA patients with unsatisfactory results after anterior callosotomy. This strategy should be considered especially in childhood cases, since obvious complication was not observed in such cases.
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PMID:[Staged total callosotomy for medically intractable seizures]. 1119 41

We report a patient with frontotemporal degeneration and parkinsonism with mental retardation. The patient was a 54-year-old man who had parkinsonism that resembled progressive supranuclear palsy, frontotemporal degeneration and myoclonus. His family included many affected members. Neuropathologically, there was degeneration of the frontal and temporal cortices, the basal ganglia, the brainstem and the cerebellum. Microscopically, neuronal loss was severe in the frontal and temporal cortex, the globus pallidus, substantia nigra, red nucleus and dentate nucleus. Fibrillary changes were found in neurons and glia that were immunostained for tau. Although we could not define the genetic abnormalities, we thought that this case might have involved frontotemporal dementia and parkinsonism linked to chromosome 17.
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PMID:A case of frontotemporal dementia and parkinsonism of early onset with progressive supranuclear palsy-like features. 1122 Jun 96

Sialidosis is an autosomal recessive disease caused by the genetic deficiency of lysosomal sialidase, which catalyzes the catabolism of sialoglycoconjugates. The disease is associated with progressive impaired vision, macular cherry-red spots, and myoclonus (sialidosis type I) or with skeletal dysplasia, Hurler-like phenotype, dysostosis multiplex, mental retardation, and hepatosplenomegaly (sialidosis type II). We analyzed the effect of the missense mutations G68V, S182G, G227R, F260Y, L270F, A298V, G328S, and L363P, which are identified in the sialidosis type I and sialidosis type II patients, on the activity, stability, and intracellular distribution of sialidase. We found that three mutations, F260Y, L270F, and A298V, which are clustered in the same region on the surface of the sialidase molecule, dramatically reduced the enzyme activity and caused a rapid intralysosomal degradation of the expressed protein. We suggested that this region might be involved in sialidase binding with lysosomal cathepsin A and/or beta-galactosidase in the multienzyme lysosomal complex required for the expression of sialidase activity. Transgenic expression of mutants followed by density gradient centrifugation of cellular extracts confirmed this hypothesis and showed that sialidase deficiency in some sialidosis patients results from disruption of the lysosomal multienzyme complex.
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PMID:Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex. 1127 74


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