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)

Linkage of the gene responsible for an X-linked early onset parkinsonism disorder with mental retardation (McKusick 311510) to DNA probes that detect restriction fragment length polymorphisms is described. The disease gene is linked to the F8C gene, and to DNA probes detecting polymorphic loci DXS52, DXS15, DXS134, and DXS374 with maximum lod scores at theta = 0 of 5.08, 5.19, 5.00, 5.03, and 4.46, respectively. Multipoint linkage analysis gives a maximum multipoint lod score of 6.75 at the F8C gene. This places the disease gene in chromosomal region Xq27.3-qter.
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PMID:Waisman syndrome, a human X-linked recessive basal ganglia disorder with mental retardation: localization to Xq27.3-qter. 167 30

Ten autopsy cases of Progressive Supranuclear Palsy (PSP) are reported. Age at onset ranged from 16 to 67 years and the duration of illness 3 to 24 years. The clinical features were aggressive mental retardation in 4 cases with early onset, paroxysmal dysequilibrium, ophthalmoplegia, rigidity and akinesia, pseudobulbar palsy and variable degrees of dementia. Neuropathology showed widespread neurofibrillary degeneration associated with system-bound neuronal loss and gliosis in subcortical areas, particularly affecting the subthalamic nucleus, substantia nigra, brainstem tegmentum and dentate nuclei, with no or little involvement of the cerebral cortex. The distribution of the lesions and the ultrastructure of the neurofibrillary tangles made of 15 nm straight filaments (seen in one case) in PSP are different from postencephalitic parkinsonism, Guam Parkinson-dementia complex and brainstem affection in (pre)senile dementia. Post-mortem biochemical analysis of two brains disclosed severe reduction of tyrosine hydroxylase, the key synthetic enzyme of the catecholamine pathway, not only in the nigrostriatal system as seen in Parkinson's disease, but in most areas of the brain-stem and limbic system. The implication and possible pathogenic and therapeutic significance of these biochemical findings are discussed. The etiology of PSP and its nosological position within the degenerative extrapyramidal disorders remain unknown.
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PMID:Progressive supranuclear palsy: clinico-pathological and biochemical studies. 610 28

A case of neurofibromatosis with varied clinical symptoms due to parental consanguinity is reported. The patient presented the following manifestations: mental retardation, curved tibias, kyphoscoliosis, basillary impression with pyramidal syndrome and parkinsonism, subluxation of the lenses, bilateral blindness, and hypogonadism. Subluxation of the lenses and hypogonadism deserve special mention because of the rarity of their presentation in this disease. The hypogonadism was of the hypogonadotrophic type without evidence of pituitary or gonadal tumor. The possible causes of endocrine dysfunction in neurofibromatosis are discussed. The more likely hypothesis explains endocrine dysfunction on the basis of an elongation of the pituitary stem; if such abnormality was caused by gliosis of the optic chiasma, an explanation would be apparent for the bilateral blindness presented by our patient since infancy. The alterations of the nervous, endocrine, and osteoarticular systems, and the ocular manifestations that can be present in von Recklinghausen's disease are also reviewed.
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PMID:[Hypogonadism, basillary impression, subluxation of the lenses, and other clinical manifestations in a case of neurofibromatosis (author's transl)]. 678 93

Familial polyneuropathy mimicking Charcot-Marie-Tooth disease associated with parkinsonism and dementia has been reported in literature. We present with similar peroneal muscular atrophy, rigidity of upper extremities, severe peripheral neuropathy, mental retardation and diabetes mellitus. The patient, a 42-year-old man, developed progressive muscle weakness, mental retardation and difficulty in walking in childhood. Because of his pes cavus, he had three surgical operations. At the age of 20 years, he developed distal muscular atrophy of lower limbs. On neurological examination, all limb muscles were atrophic, especially in lower one third of the thigh. Rigidity was noted in the upper extremities. Deep tendon reflexes were hyperactive in the upper and diminished in the lower extremities. Muscle CT revealed low density areas in all the muscles examined, specially in the gastrocnemius and anterior tibial muscles. Needle EMG showed neurogenic change in the forearm, but not in the lower limbs, because of no voluntary contractions obtained due to severe muscle atrophy. Marked slowing of motor conduction velocity with muscle action potentials of very low amplitude was found in the ulnar nerve. Muscle action potentials were not elicited in the median and peroneal nerves. Sensory action potentials were not elicited from the median, ulnar and sural nerves. These findings were consistent with axonal polyneuropathy. In the sural nerve biopsy, the densities of myelinated fibers were markedly decreased. However, unmyelinated fiber densities were relatively preserved. Onion bulb formation was not found. This patient may be classified into hereditary motor-sensory neuropathy (HMSN) type II based on the clinical findings delayed nerve conduction velocities and axonal degeneration in the sural nerve. He has also diabetes mellitus. CT of the brain revealed nothing particular. He is one of members with familial Parkinson's disease (PD) developed in Sagamihara. Peroneal muscular atrophies are not necessarily associated with PD, though it has been occasionally complicated in various neuro-degenerative diseases including parkinsonism. We are now following the patient to detect the symptom of Parkinson's disease for early treatment.
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PMID:[An unusual case of peroneal muscular atrophy with rigidity, polyneuropathy, mental retardation, and diabetes mellitus developed in familial Parkinson's disease]. 866 30

A 38 year old patient with megalencephaly, mental retardation, and lifelong tremor developed levodopa responsive parkinsonism in his mid-30s followed by the appearance of dyskinesiae, motor fluctuations, hallucinations, and dementia. Brain MRI showed, as well as other changes, iron deposition in the globus pallidus, substantia nigra, and the pulvinar of the thalamus. Postmortem examination disclosed depigmentation of the substantia nigra pars compacta with neuronal loss, gliosis, and Lewy body formation. Axonal dystrophic spheroids, neuronal loss, calcification, and iron deposition were found in the substantia nigra pars reticulata. Less severe changes without neuronal loss were seen in the globus pallidus. This combination of megalencephaly with neuroaxonal changes predominantly in the pars reticulata and Lewy body degeneration isolated to the substantia nigra pars compacta has not been previously reported.
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PMID:Atypical dopa responsive parkinsonism in a patient with megalencephaly, midbrain Lewy body disease, and some pathological features of Hallervorden-Spatz disease. 893 52

A large Swedish family with members affected by progressive external ophthalmoplegia with hypogonadism were followed-up and reviewed. Hypogonadism included delayed sexual maturation, primary amenorrhea, early menopause, and testicular atrophy. Cataracts, cerebellar ataxia, neuropathy, hypoacusia, pes cavus, tremor, parkinsonism, depression, and mental retardation were other features observed in this family. Muscle biopsy samples of advanced cases showed ragged-red fibers, focal cytochrome c oxidase deficiency, and multiple mtDNA deletions by Southern blot analysis. An autosomal dominant mode of inheritance was evident with anticipation in successive generations. Linkage analysis excluded the chromosome 10q23.3-q24.3 region reported as being linked to the disease in a Finnish family with autosomal dominant progressive external ophthalmoplegia. We report for the first time clinical evidence for anticipation in a family with autosomal dominant progressive external ophthalmoplegia. We hypothesize that the nuclear gene causing this enigmatic disorder may be directly influenced by an expansion of an unstable DNA sequence and that the resulting phenotype is caused by a concerted action with multiple deletions of mtDNA.
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PMID:Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism. 894 Dec 70

Careful clinical delineation and advances in analytical methods have opened new possibilities for the detection of inherited neurometabolic disorders, some of which require specific CSF analyses for diagnosis. Although patients suffering from these disorders have recognizable phenotypes, there are strong indications that remain many undiagnosed, leading to a continuation of futile diagnostic searches and, for most disorders, withholding of available rational therapy. As there is still widespread uncertainty about when to perform specialist CSF investigations, it is the aim of this paper to define the place for CSF investigations in the diagnostic work-up of a child with an encephalopathy of unknown origin. Most neurometabolic disorders can be identified through serum, plasma and urine analyses in conjunction with neuroradiological investigations. Whenever CSF investigations are performed, the analysis should include quantitative determination of lactate, pyruvate and amino acids, the latter by methods especially suited for CSF, in addition to cells, glucose, protein, immunoglobulin classes, specific immunoglobulins, and an evaluation of the blood-brain barrier. If the disease course is non-progressive or if extracerebral symptoms are present in addition to an encephalopathy, e.g. endocrinological, hepatic, muscular or renal symptoms, investigations of metabolites in CSF over and above lactate, pyruvate and amino acids are generally noncontributary. Specific CSF investigations, which are discussed in detail, test metabolic pathways of brain metabolism, especially of neurotransmission. For a successful diagnosis of these defects, analyses must be planned individually, before CSF samples are taken, based on family history, clinical findings and disease course. Different determinations require different logistics from taking of the sample to shipment. One indication for specialized CSF analyses including biogenic monoamines and GABA is severe neonatal/infantile epileptic encephalopathy. In addition to a therapeutic trial of B6, folinic acid should be tried empirically for two to three days as the emerging syndrome of folinic acid responsive seizures appears to be the underlying cause in a sizable proportion of patients. In later infancy and childhood, defects in the metabolism of the biogenic monoamines may be suspected in patients with (fluctuating) extrapyramidal disorders, in particular Parkinsonism dystonia or more general "athetoid cerebral palsy", and vegetative disturbances. A severe epileptic encephalopathy and progressive mental retardation may be present. Neuroimaging findings do not show specific lesions. Determinations of folates and organic acids in CSF appear at present only warrantable individually in special constellations, e.g. classical clinical findings and disease course suggestive of glutaryl-CoA dehydrogenase deficiency with repeated negative quantitative analyses of organic acids in urine. The diagnosis of disorders, which require specific analyses of CSF, can only be achieved by conscious diagnostic decisions based on a concept of the respective disease and repeated scrupolous expert clinical evaluation aided by an array of investigations in blood and urine as well as neuroimaging findings. No single one investigation in CSF can serve as a "selective screening" test. A growing awareness of these disorders is needed and should lead to increased and earlier diagnosis of patients through fewer rather than more lumbar punctures.
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PMID:Cerebrospinal fluid investigations for neurometabolic disorders. 963 60

Paternal or maternal deletions in the 15q11.2-q13 region are known to result in Prader-Willi syndrome (PWS) or Angelman syndrome (AS), respectively. Maternal duplications in 15q11.2-q13 have been found in patients with autism. A population of adults with moderate to profound mental retardation was studied to examine the usefulness of PCR based molecular methods in screening for proximal chromosome 15 abnormalities. Two hundred and eighty-five subjects were initially screened at five microsatellite markers with average heterozygosity values of 0.74 (range 0.54-0.82). Of these subjects, four had a single allele at all five loci, suggestive of a deletion or uniparental isodisomy. The four samples were further screened with additional markers located within 15q11.2-q13 as well as markers telomeric to this region. One subject had uniparental disomy (UPD) and three subjects had a deletion. To determine the parental origin of the 15q11-q13 region containing the single haplotype, samples were analysed with a newly developed methylation specific PCR technique at the SNRPN locus. Each of the four subjects showed presence of the paternal allele and absence of the maternal allele. All cases had a phenotype consistent with Angelman syndrome as expected for the level of mental retardation, but the subject with UPD was distinct from the other subjects with an absence of a history of seizures and presence of bilateral undescended testes and Parkinsonism. Although Angelman syndrome has an estimated population prevalence of 0.008%, at least 1.4% of the moderately to profoundly mentally retarded subjects screened were found to have Angelman syndrome.
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PMID:Molecular screening for proximal 15q abnormalities in a mentally retarded population. 967 96

The human Xq11-Xq21.3 region has been implicated in several inherited disorders including dystonia-parkinsonism (DYT3), sideroblastic anemia and several specific and non-specific forms of mental retardation (MR) syndromes. As part of a positional cloning effort to identify MR genes, we have generated a YAC-based transcript map. We first constructed a YAC/STS framework by extending previously published contigs. This framework map consists of a minimal set of 119 clones, covering approximately 20 Megabases (Mb) and allowing the precise ordering of 71 STSs between DXS136 and DXS472. This YAC contig was then used to define the positions of genes and expressed sequence tags (ESTs) assigned to the Xcen-Xq21.3 region. In addition to the genes previously localized to this part of the X chromosome, 18 transcription units corresponding to additional known genes or gene family members, one pseudogene and 15 novel transcripts were mapped. This transcriptional map incorporates 51 transcription units and provides a useful resource of candidate genes for some of the disorders assigned to this region of the X chromosome.
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PMID:Transcript map of the human chromosome Xq11-Xq21 region: localization of 33 novel genes and one pseudogene. 1041 31

Primary dystonias are movement disorders with dystonia as a major symptom. They are frequently inherited as Mendelian traits. There are at least eight clinically distinct autosomal dominant and two X-linked recessive forms. In addition, pedigree analyses suggest the occurrence of an autosomal recessive variant. The clinical classification is increasingly being replaced by a genetic one. To date gene loci have been identified in at least six autosomal dominant forms, i.e., in idiopathic torsion dystonia (9q34), focal dystonia (18p), adult-onset idiopathic torsion dystonia of mixed type (8p21-q22), dopa-responsive dystonia (14q22.1-q22.2), and paroxysmal dystonic choreoathetosis (2q25-q33; 1p21-p13.3). Gene loci in the X-linked recessive forms have been assigned to Xq13.1 in the X-linked dystonia parkinsonism syndrome and to Xq22 in X-linked sensorineural deafness, dystonia, and mental retardation. The disease genes have been identified in two autosomal dominant forms and in one X-linked recessive form. Mutations in a gene coding for an ATP-binding protein were detected in idiopathic torsion dystonia (DYT1), and the GTP cyclohydrolase 1 gene is mutated in dopa-responsive dystonia (DYT5). In sensorineural deafness, dystonia, and mental retardation, mutations were found in the gene DDP coding for a polypeptide of unknown function. This article reviews the clinical and molecular genetics of primary dystonias, critically discusses present findings, and proposes referring to the known forms, most of which can be distinguished by genetic criteria, as dystonias 1-12.
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PMID:Clinical and molecular genetics of primary dystonias. 1073 19


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