Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors report the clinical, neuroimaging, muscle biopsy and mtDNA findings in a patient affected by bilateral hearing loss and mental retardation since infancy, presenting at age 31 years with a rapid deterioration of mental status and ataxia leading to vegetative condition and death at the age of 32 years. Clinical and genetic studies have been also performed in the mother, affected by neurosensorial hearing loss. Muscle biopsy showed severe mitochondrial alterations in the propositus and evidence of mitochondrial alterations in his mother. Direct mtDNA sequencing in all family members revealed the known 7472insC mutation and the recently described A7472C sequence variation in the tRNA(Ser(UCN))gene. RFLP-PCR confirmed the heteroplasmic nature of the two mutations and failed to find the second transversion in 200 controls. The percentage of mutant genomes harbouring 7472insC ranged from 3 to 7% in asymptomatic family members to 70% in the proband and his mother, whereas the percentage of A7472C mutant genomes was about 90% in all maternal relatives except the proband (56%) and his sister (5%). In conclusion, this is the first report of a rapidly progressive encephalopathy in association with the 7472insC mutation in mtDNA, combined with an A>C variation at the same nucleotide with a possible suppression effect on the pathogenic mutation.
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PMID:Rapidly progressive neurodegeneration in a case with the 7472insC mutation and the A7472C polymorphism in the mtDNA tRNA ser(UCN) gene. 1636 37

Pathogenic mutations in the tRNA(Leu(UCN)) gene of mitochondrial DNA (mtDNA) have been invariably accompanied by skeletal myopathy with or without chronic progressive external ophthalmoplegia (CPEO). We report a young woman with a heteroplasmic m.12276G>A mutation in tRNA(Leu(UCN)), who had childhood-onset and slowly progressive encephalopathy with ataxia, cognitive impairment, and hearing loss. Sequencing of the 22 tRNA mitochondrial genes is indicated in all unusual neurological syndromes, even in the absence of maternal inheritance.
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PMID:Slowly progressive encephalopathy with hearing loss due to a mutation in the mtDNA tRNA(Leu(CUN)) gene. 2002 7

Perinatal hypoxia could cause long-term disturbances of the dopaminergic (DA) systems, leading to behavioral and/or neurological deficits later in life. Increased expression of tyrosine hydroxylase (TH) was shown in the substantia nigra (SN) and ventral tegmental area (VTA) of human neonates that suffered severe/acute perinatal hypoxic insults, but also in all neurons of the Edinger-Westphal nucleus (EW). Since EW, in humans, contains urocortin 1 (UCN1)/centrally projecting neurons (EWcp), we investigated: (a) the development of UCN1-positive neurons and the possible effect of neonatal hypoxic/ischemic encephalopathy on UCN1 expression and (b) the possible colocalization of UCN1 with TH in neonates with histological signs of acute hypoxic injury. Our results showed that in EWcp of the human neonate, UCN1-immunoreactivity was already evident from 34 weeks of gestation onwards at very low levels. No UCN1-immunoreactivity was found in neurons of SN or VTA. In EWcp, a positive correlation was found between UCN1 expression and the age of the neonates, but not with hypoxia neuropathological grade. UCN1 was colocalized with TH in most EWcp neurons. Since UCN1 in EWcp may play a significant role in stress adaptation and consequently in stress-related disorders, the role of catecholamine synthesis in this nucleus under acute hypoxic conditions must be further investigated.
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PMID:Immunohistochemical demonstration of urocortin 1 in Edinger-Westphal nucleus of the human neonate: colocalization with tyrosine hydroxylase under acute perinatal hypoxia. 2401 14

We describe here two novel mitochondrial mutations associated with a complex mitochondrial encephalopathy. An A to G transition at position 7495 (MT-TS1 (MT-tRNSer(UCN))) was identified at 83% heteroplasmy in the muscle of a four year old female with ptosis, hypotonia, seizures, and dilated cardiomyopathy (Case 1). A homoplasmic C to T transition at position 5577 (MT-TW (MT-tRNATrp)) was found in a twenty-four year old woman with exercise intolerance, mild muscle weakness, hearing loss, seizures, and cognitive decline (Case 2). The phenotypic information provided here will assist in phenotype-genotype correlations should additional patients be reported in the future. The mutations can be added to the database of mitochondrial DNA variations in conserved regions which result in clinically diverse phenotypes with the shared markers of mitochondrial disease.
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PMID:Two novel mitochondrial tRNA mutations, A7495G (tRNASer(UCN)) and C5577T (tRNATrp), are associated with seizures and cardiac dysfunction. 2769 65