Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten patients with inverted duplication of 8p (inv dup 8p) were studied with cytogenetic, biochemical and molecular techniques. The duplication for the region 8p12-p22 was always associated with a deletion of the locus D8S7 (mapped in 8p23.1) as demonstrated with the probe pSW50 by both in situ hybridization and Southern blot. Restriction fragment length polymorphisms detected by probes pSW50 (1 case) and by pG2LPL35 (locus LPL) (two cases) were informative as to a maternal origin of the anomaly. The activity of glutathione reductase, whose gene maps in the duplicated region at 8p21.1, was increased in all patients. The recognizable phenotype of inv dup 8p includes neonatal hypotonia, prominent forehead, large mouth with everted lower lip, abnormally shaped large ears, brain malformations and severe mental retardation. Our findings indicate that the chromosome rearrangement is homogeneous at least for the presence of the deletion and support the hypothesis of a common mechanism of origin.
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PMID:D8S7 is consistently deleted in inverted duplications of the short arm of chromosome 8 (inv dup 8p). 790 Nov 42

We report the case of a 5-year-old girl with severe developmental disabilities, skeletal anomalies, hypotonia, rectal atresia, malrotation of the intestine, horseshoe kidney, vesicoureteric reflux, and minor facial anomalies. Conventional cytogenetic techniques suggested that she had a mosaic 46,XX/47,XX,+i(8p) constitution, and the identity of the isochromosome was confirmed by in situ hybridization and chromosome painting. Polymorphic DNA markers are consistent with the i(8p) having arisen as the result of a segregation error and centromere misdivision at the second maternal meiotic division. The i(8p) was seen in 17/25 (68%) lymphocytes at the age of one month but had declined to 31/100 (31%) cells by the age of 5 years. At this time the i(8p) was seen in 30/68 (44%) cultured skin fibroblasts. The proposita had an approximately twofold increase in red cell glutathione reductase activity but a normal level of tissue-plasminogen activator. These enzyme results are consistent with the known localisation of the glutathione reductase gene on the short arm of chromosome 8 but suggest that the tissue-plasminogen activator gene may map outside this region.
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PMID:Mosaic tetrasomy 8p: molecular cytogenetic confirmation and measurement of glutathione reductase and tissue plasminogen activator levels. 836 38

Pipecolic acid (PA) levels are increased in severe metabolic disorders of the central nervous system such as Zellweger syndrome, infantile Refsum disease, neonatal adrenoleukodystrophy and hyperlysinemia. The affected individuals present progressive neurological dysfunction, hypotonia and growth retardation. The mechanisms of brain damage of these disorders remain poorly understood. Since PA catabolism can produce H2O2 by oxidases, oxidative stress may be a possible mechanism involved in the pathophysiology of these diseases. Lipoic acid (LA) is considered an efficient antioxidant and has been shown to prevent oxidative stress in experimental models of many disorders of the neurologic system. Considering that to our knowledge no study investigated the role of PA on oxidative stress, in the present work we investigated the in vitro effects of PA on some oxidative stress parameters and evaluated the LA efficacy against possible pro-oxidant effects of PA in cerebral cortex of 14-day-old rats. The activities of catalase (CAT), glutathione peroxidase (GPx), glucose 6-phosphate dehydrogenase (G6PD), and glutathione S-transferase (GST) along with reduced glutathione (GSH) content were significantly decreased, while superoxide dismutase (SOD) activity and thiobarbituric acid-reactive substances (TBA-RS) were significantly enhanced by PA. LA was able to prevent these effects by improving the activity of antioxidant enzymes, increasing GSH content and reducing TBA-RS. In contrast, glutathione reductase and 6-phosphogluconate dehydrogenase activities and sulfhydryl content were not affected. Taken together, it may be presumed that PA in vitro elicits oxidative stress and LA is able to prevent these effects.
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PMID:Pipecolic acid induces oxidative stress in vitro in cerebral cortex of young rats and the protective role of lipoic acid. 2433 30