Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027066 (myoclonus)
 4,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epilepsy affects more than 0.5% of the world's population and has a large genetic component. The most common human genetic epilepsies display a complex pattern of inheritance and the susceptibility genes are largely unknown. However, major advances have recently been made in our understanding of the genetic basis of monogenic inherited epilepsies. Progress has been particularly evident in familial idiopathic epilepsies and in many inherited symptomatic epilepsies, with the discovery that mutations in ion channel subunits are implicated, and direct molecular diagnosis of some phenotypes of epilepsy is now possible. This article reviews recent progress made in molecular genetics of epilepsy, focusing mostly on idiopathic epilepsy, and some types of myoclonus epilepsies. Mutations in the neuronal nicotinic acetylcholine receptor alpha4 and beta2 subunit genes have been detected in families with autosomal dominant nocturnal frontal lobe epilepsy, and those of two K(+) channel genes were identified to be responsible for underlying genetic abnormalities of benign familial neonatal convulsions. The voltage-gated Na(+) -channel (alpha1,2 and beta1 subunit), and GABA receptor (gamma2 subunit) may be involved in the pathogenesis of generalized epilepsy with febrile seizure plus and severe myoclonic epilepsy in infancy. Mutations of Ca(2+)-channel can cause some forms of juvenile myoclonic epilepsy and idiopathic generalized epilepsy. Based upon these findings, pathogenesis of epilepsy as a channelopathy and perspectives of molecular study of epilepsy are discussed.
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PMID:Genetics of epilepsy: current status and perspectives. 1220 89

Nova is a neuron-specific RNA binding protein targeted in patients with the autoimmune disorder paraneoplastic opsoclonus-myoclonus ataxia, which is characterized by failure of inhibition of brainstem and spinal motor systems. Here, we have biochemically confirmed the observation that splicing regulation of the inhibitory GABA(A) receptor gamma2 (GABA(A)Rgamma2) subunit pre-mRNA exon E9 is disrupted in mice lacking Nova-1. To elucidate the mechanism by which Nova-1 regulates GABA(A)Rgamma2 alternative splicing, we systematically screened minigenes derived from the GABA(A)Rgamma2 and human beta-globin genes for their ability to support Nova-dependent splicing in transient transfection assays. These studies demonstrate that Nova-1 acts directly on GABA(A)Rgamma2 pre-mRNA to regulate E9 splicing and identify an intronic region that is necessary and sufficient for Nova-dependent enhancement of exon inclusion, which we term the NISE (Nova-dependent intronic splicing enhancer) element. The NISE element (located 80 nucleotides upstream of the splice acceptor site of the downstream exon E10) is composed of repeats of the sequence YCAY, consistent with previous studies of the mechanism by which Nova binds RNA. Mutation of these repeats abolishes binding of Nova-1 to the RNA in vitro and Nova-dependent splicing regulation in vivo. These data provide a molecular basis for understanding Nova regulation of GABA(A)Rgamma2 alternative splicing and suggest that general dysregulation of Nova's splicing enhancer function may underlie the neurologic defects seen in Nova's absence.
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PMID:Nova regulates GABA(A) receptor gamma2 alternative splicing via a distal downstream UCAU-rich intronic splicing enhancer. 1280 7

Hypoxia causes dysfunction of excitatory and inhibitory neurotransmission, often resulting in encephalopathy, seizures or myoclonus. We evaluated the effects of hypoxia on GABAA receptor (GABAAR) function and expression in an in vitro model of neuronal hypoxia. NT2-N cells, derived from the human NT2 teratocarcinoma cell line, were exposed to < or =1% O2 for 8 h and then used immediately for experiments or allowed to recover under normoxic conditions (95% air/5% CO2) for 24, 48 or 96 h. Hypoxic treatment did not cause obvious morphological changes or cell death. In whole-cell patch-clamp recordings, the GABA current EC50 was unchanged, however, maximal GABA-evoked currents changed in a biphasic manner. Maximal GABA currents were significantly increased immediately after hypoxia, but were significantly reduced after 48 h normoxic recovery, and then returned to baseline after 96 h recovery. Maximal potentiation of 10 microM GABA currents by diazepam was increased 48 h after hypoxia, but potentiation by zolpidem was decreased. Barbiturate enhancement and zinc inhibition of GABA currents were unchanged. Semiquantitative reverse transcriptase (RT)-PCR showed decreased alpha1, alpha5, beta2 and gamma2 subunit mRNA after hypoxia. Hypoxic exposure altered GABAAR physiology and subunit mRNA expression, which may correlate with symptoms observed after hypoxia in vivo.
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PMID:Hypoxia alters GABAA receptor function and subunit expression in NT2-N neurons. 1497 87