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

Mutations in the SCN 1 A gene, encoding the neuronal voltage-gated sodium channel alpha1 subunit, cause SMEI, GEFS+, and related epileptic syndromes. We herein report the R1575C-SCN 1 A mutation identified in a patient with Rasmussen encephalitis. R1575C were constructed in a recombinant human SCN 1 A and then heterologously expressed in HEK293 cells along with the human beta1 and beta2 sodium channel accessory subunits. Whole-cell patch-clamp recording was used to define biophysical properties. The R1575C channels exhibited increased channel availability and an increased persistent sodium current in comparison to the wild-type. These defects of electrophysiological properties can result in neuronal hyperexitability. The seizure susceptibility allele may influence the pathogenesis of Rasmussen encephalitis in this case.
 ...
PMID:Rasmussen encephalitis associated with SCN 1 A mutation. 1803 52

The spontaneously epileptic rat (SER), a double mutant (zi/zi, tm/tm), exhibits both tonic convulsions and absence-like seizures from the age of 8 weeks. Since the first point mutation in the voltage-gated sodium channel (VGSC) beta(1) subunit in human generalized epilepsy with febrile seizures plus (GEFS+) was identified, more and more types of genetic epilepsy have been causally suggested to be related to gene changes in VGSC. However, there are no reports that can elucidate the effects of VGSC in SER. The present study was undertaken to detect sodium channel I alpha-isoform (Na(v)1.1), sodium channel III alpha-isoform (Na(v)1.3) and beta(1) subunit from both the level of mRNA and protein in SERs hippocampus compared with control Wistar rats. In this study, the mRNA expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit in SERs hippocampus were significantly higher than those in control rats hippocampus by real-time RT-PCR; The protein distributions and expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit in SERs hippocampus were detected by immunofluorescence, immunohistochemistry and western blot, and the protein expressions of Na(v)1.1, Na(v)1.3 and beta(1) subunit were significantly increased. In conclusion, our study suggested for the first time that sodium channel Na(v)1.1, Na(v)1.3 and beta(1) subunit up-regulation at the mRNA and protein levels of SER hippocampus might contribute to the generation of epileptiform activity and underlie the observed seizure phenotype in SER. The results of this study may be of value in revealing components of the molecular mechanisms of hippocampal excitation that are related to genetic epilepsy.
 ...
PMID:Voltage-gated sodium channel Nav1.1, Nav1.3 and beta1 subunit were up-regulated in the hippocampus of spontaneously epileptic rat. 1815 13

In recent years, different mutations in genes that control the excitability of neurons have been described in idiopathic childhood epilepsies. Most commonly, sodium/potassium channelopathies and GABA-receptor mutations are involved. Major progress has been made in the field of idiopathic generalised epilepsies associated with febrile seizures (GEFS+). It now is becoming clear that mutations should not only be looked for in familial cases, but also in sporadic cases, especially in infants and young children with unexplained severe epileptic encephalopathies. Many studies also define 'epilepsy susceptibility genes', which contribute to one's individual genetic vulnerability to develop epilepsy. It should be realized, however, that in the most common idiopathic benign childhood epilepsies (benign rolandic and occipital epilepsies), major breakthroughs are still awaited. In addition, a better clinical description of the epileptic phenotypes is needed to explain more precisely the genotypic and phenotypic heterogeneity. Genetic studies are nowadays becoming a necessary diagnostic step in the evaluation of idiopathic childhood epilepsies, not only in familial cases, but also in sporadic cases.
 ...
PMID:What's new in: "genetics in childhood epilepsy". 1832 Feb 21

Generalized epilepsy with febrile seizures plus (GEFS+) is a familial inherited epileptic syndrome characterized by phenotypic heterogeneity from the milder febrile seizures to the severest epileptic encephalopathy such as severe myoclonic epilepsy in infancy (SMEI). GEFS+ is a disorder with a genetic heterogeneity. Molecular genetics have revealed that four genes are associated with the pathogenesis of GEFS+. These include mutations in genes encoding subunits of neuronal voltage-gated sodium channels (SCN1A, SCN1B, SCN2A) and gamma(2) subunit of the gamma amino-butyric acid (GABA)(A) receptor (GABRG2). These genes have been confirmed as having a role in autosomal dominant GEFS+ families. In addition, the phenotypes of the affected members may depend on the types and locations of these gene mutations. This review states the molecular genetic progress of GEFS+ in brief.
 ...
PMID:[Progress in molecular genetics of generalized epilepsy with febrile seizures plus]. 1845 5

Benign familial infantile seizures (BFIS) is a dominant idiopathic epilepsy with partial and secondarily generalized seizures with age of onsetr between 3 and 12 months. Here we describe a four-generation family with some characteristic features of BFIS but with unusual clinical signs, in eight affected members with an unusual clinical phenotype. Onset was consistently between 14 and 20 months of age with clusters of complex-partial or generalized tonic-clonic seizures and a high rate of febrile seizures, which have not been described for BFIS previously. All affected members showed multifocal interictal epileptiform discharges in the EEG. The known loci for benign familial neonatal/infantile seizures (BFNS/BFNIS), generalized epilepsy with febrile seizures plus (GEFS+) and the BFIS locus on chromosome 19q were excluded. Further genetic analysis showed suggestive linkage to the major BFIS locus on chromosome 16 between markers D16S690 and D16S3136. This ;;BFIS-like'' syndrome may enlarge the phenotypic spectrum of diseases linked to the chromosome 16 region.
 ...
PMID:A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2-16q12.1. 1847 94

Generalized epilepsy with febrile seizures plus (GEFS+; MIM#604233) is a familial epilepsy syndrome characterized by phenotypic and genetic heterogeneity. It was associated with mutations in the neuronal voltage-gated sodium channel subunit gene (SCN1A, SCN2A, SCN1B) and ligand-gated gamma aminobutyric acid receptors genes (GABRG2, GABRD). We investigated the roles of SCN1A, SCN1B, and GABRG2 mutations in the etiology of Chinese GEFS+ families. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood lymphocytes of 23 probands and their family members. The sequences of SCN1A, SCN1B, and GABRG2 genes were analyzed by polymerase chain reaction (PCR) and direct sequencing. The major phenotypes of affected members in the 23 GEFS+ families exhibited FS and FS+, whereas rare phenotypes afebrile generalized tonic-clonic seizures (AGTCS), myoclonic-astatic epilepsy (MAE), and partial seizures were also observed. A novel SCN1A mutation, p.N935H, was identified in one family and another novel mutation in GABRG2, p.W390X, in another family. However, no SCN1B mutation was identified. The combined frequency of SCN1A, SCN1B, and GABRG2 mutations was 8.7% (2/23), extending the distribution of SCN1A and GABRG2 mutations to Chinese GEFS+ families. There were still unidentified genes contributing to the pathogenesis of GEFS+.
 ...
PMID:SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus. 1856 37

This report describes a 4-year-old male patient experienced prolonged febrile seizures after 1 year of age, multiple febrile seizures and complex partial seizures with secondary generalization. The gene encoding voltage-gated sodium channel alpha1-subunit: SCN1A analysis revealed a heterozygous de novo one-point mutation (IVS16+2 T>C) at a splice-acceptor site. This mutation was inferred to cause truncation of the alpha1-subunit molecule and, thereby, a loss of channel function. To date, truncation mutation has been found exclusively in patients with severe myoclonic epilepsy in infancy (SMEI), although only missense mutations have been found in generalized epilepsy with febrile seizures plus (GEFS+), partial epilepsy with FS+, FS+, and FS. The patient's phenotype is consistent with that of partial epilepsy with FS+, rather than SMEI, including borderline SMEI (SMEB). We present the first case report of partial epilepsy with FS+ associated with a truncation mutation of SCN1A. The possibility exists for concomitant involvement of multiple genes other than SCN1A for seizure phenotypes.
 ...
PMID:Novel de novo splice-site mutation of SCN1A in a patient with partial epilepsy with febrile seizures plus. 1863 34

Familial febrile seizures occur in both generalized epilepsy with febrile seizures plus (GEFS+) and autosomal dominant febrile seizures (ADFS). The literature largely separates families with GEFS+ from those with ADFS. However, there is clinical overlap, and families with ADFS also include individuals with afebrile seizures. The phenotypic spectrum of GEFS+ is broader now than when first described, resulting in unclear boundaries between these two familial syndromes. The purpose of this report is to highlight the phenotypic similarities of GEFS+ and ADFS. A multigenerational family with febrile and afebrile seizures is described and the clinical features are compared to those of previously reported GEFS+ and ADFS families. This family meets the requirements for both ADFS and the broader definition of GEFS+. Linkage analysis has shown no clear linkage to known febrile seizure or GEFS+ loci. Despite locus heterogeneity, identified mutations in reported GEFS+ have so far all been in sodium channel or gamma-aminobutyric acid (GABA)-receptor genes, with other modifier genes postulated to affect individual phenotypes. The two mutations identified in families with ADFS are in genes implicated in GEFS+, SCN1A, and GABRG2. We conclude that it is inappropriate to separate GEFS+ and ADFS at present given the clinical and genotypic overlap.
 ...
PMID:A case report of a family with overlapping features of autosomal dominant febrile seizures and GEFS+. 1905 98

Febrile seizures (FS) represent the most common form of childhood seizures. They affect 2-5% of infants in the Caucasian population and are even more common in the Japanese population, affecting 6-9% of infants. Some familial FS are associated with a wide variety of afebrile seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS, atypical FS (FS+) and afebrile seizures. A significant genetic component exists for susceptibility to FS and GEFS+: extensive genetic studies have shown that at least nine loci are responsible for FS. Furthermore, mutations in the voltage-gated sodium channel subunit genes (SCN1A, SCN2A and SCN1B) and the GABA(A) receptor subunit genes (GABRG2 and GABRD) have been identified in GEFS+. However, the causative genes have not been identified in most patients with FS or GEFS+. Common forms of FS are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Recently, several association studies on FS have been reported, but the results vary among different groups and no consistent or convincing FS susceptibility gene has emerged. Herein, we review the genetic data reported in FS, including the linkage analysis, association studies, and genetic abnormalities found in the FS-related disorders such as GEFS+ and severe myoclonic epilepsy in infancy.
 ...
PMID:Progress in searching for the febrile seizure susceptibility genes. 1920 61

Dravet syndrome and genetic epilepsy with febrile seizures plus (GEFS+) can both arise due to mutations of SCN1A, the gene encoding the alpha 1 pore-forming subunit of the sodium channel. GEFS+ refers to a familial epilepsy syndrome where at least two family members have phenotypes that fit within the GEFS+ spectrum. The GEFS+ spectrum comprises a range of mild to severe phenotypes varying from classical febrile seizures to Dravet syndrome. Dravet syndrome is a severe infantile onset epilepsy syndrome with multiple seizure types, developmental slowing and poor outcome. More than 70% of patients with Dravet syndrome have mutations of SCN1A; these include both truncation and missense mutations. In contrast, only 10% of GEFS+ families have SCN1A mutations and these comprise missense mutations. GEFS+ has also been associated with mutations of genes encoding the sodium channel beta 1 subunit, SCN1B, and the GABA(A) receptor gamma 2 subunit, GABRG2. The phenotypic heterogeneity that is characteristic of GEFS+ families is likely to be due to modifier genes. Interpretation of the significance of a SCN1A missense mutation requires a thorough understanding of the phenotypes in the GEFS+ spectrum whereas a de novo truncation mutation is likely to be associated with a severe phenotype. Early recognition of Dravet syndrome is important as aggressive control of seizures may improve developmental outcome.
 ...
PMID:Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus? 1920 56


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>