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)

Cells from Cockayne's syndrome (CS) patients are sensitive to ultraviolet light and defective in preferential repair of the transcribed DNA strand. CS patients suffer from complex clinical symptoms, including severe growth retardation, neurological degeneration, mental retardation, and cachexia. Two CS complementation groups, CSA and CSB, have been identified so far. RAD26 encodes the yeast counterpart of the CSB gene. Here, we purify Rad26 protein to near homogeneity from yeast cells and show that it is a DNA-dependent ATPase. In contrast to the Mfd protein that functions in transcription-coupled repair in Escherichia coli, and which is a weak and DNA independent ATPase, Rad26 is a much more active ATPase, with a strict dependence on DNA. The possible role of Rad26 ATPase in the displacement of stalled RNA polymerase II from the site of the DNA lesion and in the subsequent recruitment of a DNA repair component is discussed.
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PMID:RAD26, the yeast homolog of human Cockayne's syndrome group B gene, encodes a DNA-dependent ATPase. 870 68

We report an autopsy case of Cockayne syndrome (CS). A 40-year-old Japanese woman was admitted to our hospital for cachexia. She had displayed the striking features of CS, including dwarfism, mental retardation, neural deafness, ataxia, intracranial calcifications, and progeria since her childhood. Endocrinological examinations suggested normal pituitary function and a disorder of the hypothalamus or the cerebrum. She died of acute pneumonia at the age of 42. Autopsy findings showed typical abnormalities in the central nervous system compatible with CS; however, no atherosclerotic change was observed in the systemic arteries.
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PMID:An adult case of Cockayne syndrome without sclerotic angiopathy. 926 Jul 74

Cockayne s syndrome is a genetic disorder with a recessive autosomal inheritance, described first by Cockayne in 1936. Patients with this syndrome present failure to thrive, short stature, premature aging, neurological alterations, photosensitivity, delayed eruption of the primary teeth, congenitally absent of some permanent teeth, partial macrodontia, atrophy of the alveolar process and caries. It could be caused by two gene mutations, CNK1 (ERCC8) and ERCC6, located on the 5 and 10 chromosomes respectively, causing two variations of Cockayne s syndrome, CS-A, secondary to a ERCC8 mutation and CS-B with ERCC6 mutation, the last one causes hypersensitivity to the ultraviolet light secondary to a DNA repair defect. The syndrome is also associated with mutations of the XPB, XPD and XPG genes. In this report we present a 9 year and 4 month old patient. He had a height of 94 cm, weight of 8.6 Kg, head circumference of 42 cm. and blood pressure of 120/80. Cachectic habitus, kyphosis, microcephaly, oval face, sunken eyes, a thin and beaklike nose, lack of subcutaneous facial fat (especially in the middle of the face), and large ears give the patient a birdlike appearance. It is notorious the photosensitivity in all the sun-exposed skin. The patient also displays delayed psychomotor skills and mental retardation. In the oral cavity we found deficient hygiene, gingivitis, cervical caries, enamel hipoplasia, abnormal position of the upper and inferior lateral incisors, macrodontia of the upper central teeth, the left one presented a caries. In the x-ray we observed congenital absence of 14, 23 and 24 teeth and mandibular hipoplasia. The aim of this review is to show the dentistry community the characteristics of the Cockayne s syndrome by means of a clinical case.
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PMID:Cockayne's syndrome: a case report. Literature review. 1664 59

Cockayne syndrome and xeroderma pigmentosum-Cockayne syndrome complex are rare autosomal recessive disorders with poorly understood biology. They are characterized by profound postnatal brain and somatic growth failure and by degeneration of multiple tissues resulting in cachexia, dementia, and premature aging. They result in premature death, usually in childhood, exceptionally in adults. This study compares the clinical course and pathology of a man with Cockayne syndrome group A who died at age 31(1/2) years with 15 adequately documented other adults with Cockayne syndrome and 5 with xeroderma pigmentosum-Cockayne syndrome complex. Slowing of head and somatic growth was apparent before age 2 years, mental retardation and slowly progressive spasticity at 4 years, ataxia and hearing loss at 9 years, visual impairment at 14 years, typical Cockayne facies at 17 years, and cachexia and dementia in his twenties, with a retained outgoing personality. He experienced several transient right and left hemipareses and two episodes of status epilepticus following falls. Neuropathology disclosed profound microencephaly, bilateral old subdural hematomas, white-matter atrophy, tigroid leukodystrophy with string vessels, oligodendrocyte proliferation, bizarre reactive astrocytes, multifocal dystrophic calcification that was most marked in the basal ganglia, advanced atherosclerosis, mixed demyelinating and axonal neuropathy, and neurogenic muscular atrophy. Cellular degeneration of the organ of Corti, spiral and vestibular ganglia, and all chambers of the eye was severe. Rarely, and for unexplained reasons, in some patients with Cockayne syndrome the course is slower than usual, resulting in survival into adulthood. The profound dwarfing, failure of brain growth, cachexia, selectivity of tissue degeneration, and poor correlation between genotypes and phenotypes are not understood. Deficient repair of DNA can increase vulnerability to oxidative stress and play a role in the premature aging, but why patients with mutations in xeroderma pigmentosum genes present with the Cockayne syndrome phenotype is still not known.
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PMID:Cockayne syndrome in adults: review with clinical and pathologic study of a new case. 1709 72

Cockayne syndrome (CS) is a rare genetic disease characterized by severe growth, mental retardation and pronounced cachexia. CS is most frequently due to mutations in either of two genes, CSB and CSA. Evidence for a role of CSB protein in the repair of oxidative DNA damage has been provided recently. Here, we show that CSA is also involved in the response to oxidative stress. CS-A human primary fibroblasts and keratinocytes showed hypersensitivity to potassium bromate, a specific inducer of oxidative damage. This was associated with inefficient repair of oxidatively induced DNA lesions, namely 8-hydroxyguanine (8-OH-Gua) and (5'S)-8,5'-cyclo 2'-deoxyadenosine. Expression of the wild-type CSA in the CS-A cell line CS3BE significantly decreased the steady-state level of 8-OH-Gua and increased its repair rate following oxidant treatment. CS-A cell extracts showed normal 8-OH-Gua cleavage activity in an in vitro assay, whereas CS-B cell extracts were confirmed to be defective. Our data provide the first in vivo evidence that CSA protein contributes to prevent accumulation of various oxidized DNA bases and underline specific functions of CSB not shared with CSA. These findings support the hypothesis that defective repair of oxidative DNA damage is involved in the clinical features of CS patients.
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PMID:The role of CSA in the response to oxidative DNA damage in human cells. 1729 71

Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N-acetyl-alpha-D-glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18-63 years old. Apart from the youngest, they had lost mobility at 36-68 years. Most had developed physical problems, in particular in the 4th-6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS.
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PMID:Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems? 1764 47

Pyrimidine diseases result from deficiencies in pyrimidine de novo synthesis, degradation, and salvage pathways. Enzymatic deficiencies in pyrimidine catabolism lead to mitochondrial neurogastrointestinal encephalopathy (MNGIE), pyrimidinuria, dihydropyrimidinuria, ureidopropionic aciduria, and other disorders. While MNGIE presents with gastrointestinal dysmotility, cachexia, and leukoencephalopathy, pyrimidinuria and dihydropyrimidinuria may show symptoms of epilepsy, autism, mental retardation, and dysmorphic features. The application of HPLC-MS/MS facilitates rapid screening of pyrimidine metabolites. Here we describe an LCMS method for determination of uracil, thymine, thymidine, dihydrouracil, and dihydrothymine that are diagnostic biomarkers of MNGIE, pyrimidinuria, and dihydropyrimidinuria.
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PMID:Urine Pyrimidine Metabolite Determination by HPLC Tandem Mass Spectrometry. 2660 35