Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Voltage-gated sodium channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian sodium channels are heterotrimers, composed of a central, pore-forming alpha subunit and two auxiliary beta subunits. The alpha subunits form a gene family with at least 10 members. Mutations in alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode sodium channel beta subunits with at least one alternative splice product. A mutation in the beta 1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS + 1) in a human family with this disease. Sodium channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure-function studies have resulted in the preliminary assignment of functional domains in the beta 1 subunit. A sodium channel signaling complex is proposed that involves beta subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTP beta, and extracellular matrix molecules such as tenascin.
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PMID:Sodium channel beta subunits: anything but auxiliary. 1148 43

Voltage-gated Na+ channels are glycoprotein complexes responsible for initiation and propagation of action potentials in excitable cells such as central and peripheral neurons, cardiac and skeletal muscle myocytes, and neuroendocrine cells. Mammalian Na+ channels are heterotrimers, composed of a central, pore-forming a subunit and two auxiliary beta subunits. The a subunits form a gene family with at least 10 members. Mutations in alpha subunit genes have been linked to paroxysmal disorders such as epilepsy, long QT syndrome, and hyperkalaemic periodic paralysis in humans, and motor endplate disease and cerebellar ataxia in mice. Three genes encode Na + channel beta subunits with at least one alternative splice product. A mutation in the beta1 subunit gene has been linked to generalized epilepsy with febrile seizures plus type 1 (GEFS+1) in a human family with this disease. Na+ channel beta subunits are multifunctional. They modulate channel gating and regulate the level of channel expression at the plasma membrane. More recently, they have been shown to function as cell adhesion molecules in terms of interaction with extracellular matrix, regulation of cell migration, cellular aggregation, and interaction with the cytoskeleton. Structure-function studies have resulted in the preliminary assignment of functional domains in the beta1 subunit. A Na+ channel signalling complex is proposed that involves beta subunits as channel modulators as well as cell adhesion molecules, other cell adhesion molecules such as neurofascin and contactin, RPTPbeta, and extracellular matrix molecules such as tenascin.
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PMID:Beta subunits: players in neuronal hyperexcitability? 1177 42

Congenital long QT syndrome (LQTS) is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). As a result of these arrhythmias, patients suffer from recurrent syncopes, seizures, or sudden death as the most dramatic event. Mutations in five genes, encoding cardiac ion channels, have been identified in LQTS. Two potassium-channel genes, KCNQ1 (LQT1) and KCNH2 (LQT2 or HERG), are frequently involved in LQTS. Potassium-channel defects account for approximately 50-60% of LQTS. As patients benefit from preventive medication, early detection of a genetic defect is desired to identify the family members at risk. Speed and sensitivity of mutation detection was improved by applying the denaturing high performance liquid chromatography (DHPLC) technique for analysis of the entire KCNQ1 and KCNH2 genes and the protein encoding part of the KCNE1 and KCNE2 genes. By using this methodology, seven missense mutations in the KCNQ1 gene and nine mutations (four missense, two nonsense, one insertion, and two deletions) in the KCNH2 gene have been identified in a total number of 32 index patients diagnosed with LQTS syndrome. We conclude that this method is suitable for rapid identification of LQT gene defects due to the combination of automation, high throughput, sensitivity, and short time of analysis.
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PMID:DHPLC analysis of potassium ion channel genes in congenital long QT syndrome. 1240 36

Prolonged QT syndrome may be either congenital, as in Jervell and Lange-Nielsen or Romano-Ward syndromes, or acquired in nature. Affected children are at risk for syncope, seizures, dysrhythmias and sudden death. Physicians should consider long QT syndrome (LQTS) in all patients who present with syncope. A thorough personal and family history should be documented, with particular attention to prior syncopal episodes, congenital deafness, and unexplained sudden death. Syncope that is either recurrent or induced by exercise or stress is concerning and also should be noted. An electrocardiogram with manual calculation of the QT interval should be performed on all patients with a suggestive history. Furthermore, the diagnosis of LQTS warrants evaluation of all other family members. With recognition and appropriate treatment of affected patients, the potentially fatal consequences of LQTS may be prevented.
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PMID:Prolonged QT syndrome in children: an uncommon but potentially fatal entity. 1260 48

A-10-year-old child admitted with repeated seizures due to the long QT syndrome is described. The cardiac origin of the epilepsy was suggested by the fact that during the episode of convulsions his peripheral pulses were not palpable.
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PMID:Long QT syndrome manifesting as pulseless epilepsy. 1261 62

Previous studies have identified mutations in five ion channel genes as a cause of long QT syndrome, a heterogeneous disorder characterized by prolongation of the QT interval, multiform ventricular tachycardia (torsades de pointes), seizures, syncope, and sudden death. However, in these studies, the average age of initial symptoms is in the third decade of life or later, and few reports have described the genetic causes of long QT syndrome presenting in the prenatal or neonatal period. We used a candidate gene approach to identify the genetic cause of long QT syndrome in an infant whose initial manifestations were detected in utero. Direct bidirectional sequencing of long QT syndrome genes identified a previously unreported HERG missense mutation (R752Q). Three asymptomatic family members were heterozygous for R752Q, and the proband, who manifested ventricular tachycardia in utero, was homozygous. R752Q was not found in 100 normal unrelated chromosomes. Paternal DNA was unavailable for testing. Transient transfection of HERG generated robust IKr, but no current was observed for the mutant HERG. The HERG mutant, R752Q, is associated with a mild phenotype, inasmuch as family members with a heterozygous mutation appear unaffected. The homozygous mutation results in absence of functional IKr, causing a profound loss of HERG channel function, creating the equivalent of a "HERG knockout" and leading to a severe phenotype.
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PMID:Clinical, genetic, and biophysical characterization of a homozygous HERG mutation causing severe neonatal long QT syndrome. 1262 Nov 27

When a previously healthy, middle-aged patient presents with apparent seizures, what should alert the physician to the possibility of underlying cardiac disease? This report describes a case of long QT syndrome, initially presenting as seizures, which expressed itself at an atypically advanced age as a result of cocaine use, global myocardial ischemia, and ventricular tachycardia.
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PMID:Fatal case of delayed repolarization due to cocaine abuse and global ischemia. 1268 1

Long QT Syndrome (LQTS) is a cardiac disease characterized by a prolonged QT interval on a surface electrocardiogram (ECG) and by clinical symptoms such as seizures, syncope, and cardiac sudden death. At present, causal mutations of LQTS have been identified in five cardiac ion-channel genes. Because a causal mutation is usually unique to a specific family and can be located in any region of any of these five genes, a mutation analysis effort may require screening of the complete coding regions of each of these genes. The causative nature of a detected mutation can then be determined either by family history or by functional studies, such as the electrophysiological signature of the mutation. Here we describe a mutation analysis of an LQTS patient who carries two heterozygous missense mutations in two different LQTS genes. The first mutation identified, A572D in SCN5A, was not linked with clinical LQTS features in the two other mutation carriers in the family; neither was it identified in 90 healthy controls. Therefore, this mutation most likely has either a mild effect on cardiac ion-channel function or represents a very rare polymorphism. The second mutation, V254M in KCNQ1, co-segregated with higher QT intervals and symptoms in other family members, and was previously reported in another LQTS family. Because the clinical LQTS symptoms are most pronounced in the proband, a combined effect of both mutations cannot be excluded, although no functional data are available to support such an hypothesis. We conclude that, for newly presented LQTS cases, a mutation analysis strategy should routinely screen the complete coding region of all LQTS genes, followed by an evaluation of the identified mutation(s) in conjunction with family or functional data.
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PMID:Mutation analysis in congenital Long QT Syndrome--a case with missense mutations in KCNQ1 and SCN5A. 1282 Jul 4

Multiple mutations in several ion channel genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, and KCNJ2) have been shown to cause autosomal dominant long QT syndrome (LQTS), a familial cardiac disorder that causes syncope, seizures, and sudden death. Due to their multiple loci and considerable size, mutation detection in these genes represents a challenge that is only partially met by the conventional screening method of single-stranded conformational polymorphism (SSCP). The recently introduced denaturing high-performance liquid chromatography (dHPLC) offers a promising new method for a fast and sensitive analysis of PCR-amplified DNA fragments. To test the applicability of dHPLC in the molecular diagnosis of LQTS, we first assessed a cohort of 192 patients from our International LQTS Registry for 14 previously identified mutations (including 10 different missense mutations, 1-bp, 2-bp, 3-bp, and 9-bp deletion mutations), and 2 polymorphisms in the LQTS potassium and sodium channel genes. Applying empirically determined exon-specific melting profiles, all mutations (including four previously undetectable by SSCP) were readily identified by dHPLC. We conclude that the dHPLC technology is a highly sensitive and efficient method for the molecular analysis of LQTS, and the same PCR amplicons developed for SSCP testing can be directly used for dHPLC assay.
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PMID:Denaturing high-performance liquid chromatography quickly and reliably detects cardiac ion channel mutations in long QT syndrome. 1464 2

Long QT syndrome is a malfunction of cardiac ion channels resulting in impaired ventricular repolarization that can lead to a characteristic polymorphic ventricular tachycardia known as torsades de pointes. Stressors, by increasing sympathetic tone, and drugs can provoke torsade de pointes, leading to syncope, seizures, or sudden cardiac death in these patients. Beta blockade, implantation of cardioverter defibrillators, and left cardiac sympathetic denervation are used in the treatment of these patients. However, these treatment modalities do not guarantee the prevention of sudden cardiac death. Certain drugs, including anesthetic agents, are known to contribute to QT prolongation. After reviewing the literature the authors give recommendations for the anesthetic management of these patients in the perioperative period.
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PMID:Anesthesia for patients with congenital long QT syndrome. 1630 53


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