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 pathology of the central nervous system (CNS) in a dog with giant axonal neuropathy (GAN) is presented. Swollen axons containing excessive and disorganised neurofilaments were present in the spinal cord, mainly at the distal portions of long tracts. The fasiculus gracilis and dorsal spinocerebellar tracts were affected only in the rostral cervical cord while the lateral cortico spinal tract was principally involved in the lower thoracic and lumbar cord. Occasional swellings were also found in the central dorsal columns of the rostral lumbar segments and in the dorsal and intermediate grey matter. The nuclei gracilis and cuneatus, restiform body and ventral spinocerebellar tracts were all involved in the brain stem. Spheroids were seen in the white matter of the rostral cerebellar vermis and in the granule cell layer. The brachium of the superior colliculus contained swollen axons and the cortex was diffusely involved with spheroids. The distribution was of a distal axonopathy and the cortical changes provided an explanation for the abnormal EEG and mental retardation found in some human patients.
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PMID:The central nervous system in canine giant axonal neuropathy. 22 61

The authors describe a 25-year-old woman with giant axonal neuropathy (GAN) and severe CNS involvement. She had been admitted to hospital with generalized seizures, and had gait disturbances followed by progressive mental deterioration since childhood. Neurological examination revealed mental retardation, scanning speech, cerebellar dysfunction, pyramidal signs, mainly in the lower extremities, and peripheral sensory neuropathy. Sensory nerve conduction velocity was decreased; brain CT and MRI showed diffuse demyelination. Sural nerve biopsy revealed characteristic signs of GAN. The patient's older sister had died at the age of 23, after having had similar neurological disturbances since childhood. This case illustrates an unfamiliar presentation of GAN, characterized by mild sensory neuropathy and serve CNS involvement, including seizures.
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PMID:Giant axonal neuropathy with predominant central nervous system manifestations. 131 Feb 92

First reported in 1972 by Berg & colleagues, giant axonal neuropathy is a generalized disorder of cytoplasmic intermediate filaments affecting the nervous system particularly. The condition was originally thought to be a disorder of the peripheral nervous system, but clinical and pathological evidence has now accumulated which indicates that the brain and spinal cord are progressively involved. Over 20 cases have been reported to date. All cases reported have developed clumsiness and progressive weakness with hyporeflexia in the first seven years of life. Later dysarthria, cerebellar signs and pyramidal tract disturbances appear. Mental retardation, dementia and seizures are sometimes seen. Tightly curled hair is characteristic of, but not invariably present in, the condition. This disorder, as well as a similar condition affecting dogs, appears to be transmitted by autosomal recessive inheritance. No treatment is effective. Most cases are wheelchair bound or dead by the end of the second decade.
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PMID:Giant axonal neuropathy. A review. 254 97

We report a case of giant axonal neuropathy in a 14 year-old turkish boy with progressive chronic neuropathy and central involvement with mental retardation. CT showed a low density and MRI imaging multiple cavities and hypersignals of the white matter. Nerve and skin biopsies revealed an accumulation of neurofilaments in axonal swellings and an accumulation of intermediate filaments in fibroblasts, Schwann cells, endothelial cells. These findings are in accordance with the reported cases. Giant axonal neuropathy results from a generalized disorder of the intermediate filaments, but the precise biochemical defect is unknown. We would agree with Maia (1988) to name this affection "Giant Axonal Disease".
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PMID:[Giant axonal neuropathy: intermediate filament disease with involvement of the peripheral and central nervous system]. 266 38

Giant axonal neuropathy in two siblings was reported. The fact that two cases are found in the same family supports this disorder is genetically determined and recessively inherited. These two cases, similar to the cases reported in literature, had chronic peripheral neuropathy and CNS symptoms, and also petit mal absence and mental retardation in elder sister (case 1) and precocious puberty in younger sister (case 2). Sural nerve biopsies in both cases disclosed axonal swellings or giant axons filled with aggregated neurofilaments, and that aggregated intermediate-sized filaments were found within cytoplasm of Schwann cells, endothelial cells of intra and extra-neurial capillaries and of extra-neurial arterioles, perineurial cells and endoneurial fibroblasts. Skin biopsies in both cases disclosed that aggregated intermediate-sized filaments were also found within cytoplasm of fibroblasts, Langerhans' cells, melanocytes and endothelial cells of capillaries, lymphatic vessels and arterioles. The diagnosis of giant axonal neuropathy can be made only by the findings in skin biopsy.
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PMID:Giant axonal neuropathy: report of two siblings with endocrinological and histological studies. 680 37

The related high molecular mass microtubule-associated proteins (MAPs) MAP1A and MAP1B are predominantly expressed in the nervous system and are involved in axon guidance and synaptic function. MAP1B is implicated in fragile X mental retardation, giant axonal neuropathy, and ataxia type 1. We report the functional characterization of a novel member of the microtubule-associated protein 1 family, which we termed MAP1S (corresponding to sequence data bank entries for VCY2IP1 and C19ORF5). MAP1S contains the three hallmark domains of the microtubule-associated protein 1 family but hardly any additional sequences. It decorates neuronal microtubules and copurifies with tubulin from brain. MAP1S is synthesized as a precursor protein that is partially cleaved into heavy and light chains in a tissue-specific manner. Heavy and light chains interact to form the MAP1S complex. The light chain binds, bundles, and stabilizes microtubules and binds to actin. The heavy chain appears to regulate light chain activity. In contrast to MAP1A and MAP1B, MAP1S is expressed in a wide range of tissues in addition to neurons and represents the non-neuronal counterpart of this cytolinker family.
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PMID:Microtubule-associated protein 1S, a short and ubiquitously expressed member of the microtubule-associated protein 1 family. 1552 9

Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase associated neurodegeneration (PKAN), an autosomal recessive (AR) disorder characterized by motor symptoms as such as dystonia or parkinsonism, mental retardation, retinitis pigmentosa and iron accumulation in the brain. As many neurodegenerative conditions have similar clinical features we screened a number of adult and childhood onset movement disorders for PANK2 mutation. This included cases with neurodegeneration and brain iron accumulation, corticobasal degeneartion, progressive supranuclear palsy (PSP), Parkinson's disease (PD), multiple system atropy, giant axonal neuropathy (GAN), neuroaxonal dystrophy (NAD), Guam dementia and HARP syndrome (pallido-pyramidal syndrome and hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa and pallidal degeneration). From our series of patients one patient with PKAN and a progressive severe dystonic syndrome, cerebellar ataxia, retinitis pigmentosa and eventual anarthria had a novel combination of two compound heterozygote mutations identified in the PANK2 gene, G-->A transition at base 1238 (G411R) and a C-->A transition at base 1184 (A395E). In the patient with HARP syndrome two compound heterozygote mutations (Met327Thr and IVS5-1 G to T) in the PANK2 gene were found. No other mutations were found in any of the other patient groups, suggesting that PANK2 mutations are not associated with the aetiology of these adult degenerative conditions and confirms the genetic heterogeneity in neurodegeneration with brain iron accumulation.
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PMID:PANK2 gene analysis confirms genetic heterogeneity in neurodegeneration with brain iron accumulation (NBIA) but mutations are rare in other types of adult neurodegenerative disease. 1696 35

Giant axonal neuropathy is a rare autosomal recessive disorder, which typically involves both central and peripheral nervous system. Yet the phenotypic-genotypic correlation remains obscure. We report a novel compound heterozygous mutation with the c. 805C>T in exon 4(Arg545His missense mutation) and the c. 1634G>A in exon 11(Arg269Trp missense mutation) in an 11-year-old Chinese giant axonal neuropathy case. This patient had an atypical giant axonal neuropathy phenotype rather similar to Charcot-Marie-Tooth disease, without tightly curled hair and mental retardation. The patient had a slowly progressive sensory motor neuropathy since age 3 years, and she also had nystagmus, feet deformities, scoliosis, and cerebellar tonsillar protrusion. Electrophysiological studies indicated a predominantly axonal sensory-motor neuropathy. The diagnosis was confirmed by sural nerve biopsy and direct sequencing of all the 11 gigaxonin exons. The proband's parents are heterozygotes of the disease without symptoms. Our findings extend the number of gigaxonin mutations that cause giant axonal neuropathy.
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PMID:Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene. 2324 52