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)

Mutations in the gene encoding the gamma2 subunit of the gamma-aminobutyric acid type A receptor (GABRG2) have been reported to cause childhood absence epilepsy (CAE), febrile seizures (FS), and generalized epilepsy with FS plus (GEFS+). The authors analyzed GABRG2 in 47 unrelated patients with CAE, FS, and GEFS+ and identified a novel mutation that cosegregated with FS. Electrophysiologic studies demonstrated altered current desensitization and reduced benzodiazepine enhancement in mutant receptors.
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PMID:A novel GABRG2 mutation associated with febrile seizures. 1692 25

Establishing an etiologic diagnosis in adults with refractory epilepsy and intellectual disability is challenging. We analyzed the phenotype of 14 adults with severe myoclonic epilepsy of infancy. This phenotype comprised heterogeneous seizure types with nocturnal generalized tonic-clonic seizures predominating, mild to severe intellectual disability, and variable motor abnormalities. The diagnosis was suggested by a characteristic evolution of clinical findings in the first years of life. Ten had mutations in SCN1A and one in GABRG2.
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PMID:Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults. 1719 Sep 49

Early onset of absence seizures (<3 years) is rare and usually associated with a poor cognitive prognosis. Familial cases have not been reported to date. We observed a family in which two out of three sibs showed early-onset absences and mild mental retardation. Linkage to the ECA1 locus, where one clinical subtype of CAE is mapped, was excluded by haplotype analysis. Direct sequencing of the candidate genes CLCN2 ,GABRG2 and CHRNA4 showed no mutations. We suggest the possibility of a specific epileptic syndrome with a putative AR inheritance. Further report of affected patients might allow a better classification.
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PMID:Familial occurrence of early-onset childhood absence epilepsy. 1726 50

We attempted to identify the prevalence of the R188W mutation of the SCN2A gene and the K289M mutation and single-nucleotide polymorphism rs211014 of the GABRG2 gene in children of southern China who have febrile seizures. Neither mutation was found in our subjects. The single-nucleotide polymorphism rs211014 AA genotype was overrepresented in the febrile-seizures group compared with controls (62.4% vs 29.0%). The single-nucleotide polymorphism rs211014 A allele was higher in the febrile-seizures group (P < .005). Compared with the single-nucleotide polymorphism rs211014 CC genotype, the odds ratio for developing febrile seizures in individuals with the single-nucleotide polymorphism rs211014 AA genotype was 4.05 (P < .005). A new mutation of C-to-T transition was found at nucleotide 81719 of the GABRG2 gene in a 5-year-old boy, suggesting that the above mutations may not be the main disease mutations. The single-nucleotide polymorphism rs211014 A allele may predict susceptibility to febrile seizures.
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PMID:Association analysis of gamma2 subunit of gamma-aminobutyric acid (GABA) type A receptor and voltage-gated sodium channel type II alpha-polypeptide gene mutation in southern Chinese children with febrile seizures. 1764 Dec 56

In recent years, progress in understanding the genetic basis of idiopathic generalized epilepsies has proven challenging because of their complex inheritance patterns and genetic heterogeneity. Genetic polymorphisms offer a convenient avenue for a better understanding of the genetic basis of idiopathic generalized epilepsy by providing evidence for the involvement of a given gene in these disorders, and by clarifying its pathogenetic mechanisms. Many of these genes encode for some important central nervous system ion channels (KCNJ10, KCNJ3, KCNQ2/KCNQ3, CLCN2, GABRG2, GABRA1, SCN1B, and SCN1A), while many others encode for ubiquitary enzymes that play crucial roles in various metabolic pathways (HP, ACP1, ME2, LGI4, OPRM1, GRIK1, BRD2, EFHC1, and EFHC2). We review the main genetic polymorphisms reported in idiopathic generalized epilepsy, and discusses their possible functional significance in the pathogenesis of seizures.
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PMID:Genetic polymorphisms and idiopathic generalized epilepsies. 1776 2

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.
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PMID:[Progress in molecular genetics of generalized epilepsy with febrile seizures plus]. 1845 5

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+.
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PMID:SCN1A, SCN1B, and GABRG2 gene mutation analysis in Chinese families with generalized epilepsy with febrile seizures plus. 1856 37

Mutations of SCN1A, encoding the voltage-gated sodium channel alpha1 subunit, represent the most frequent genetic cause of severe myoclonic epilepsy in infancy (SMEI). The purpose of this study was to determine if mutations in other seizure susceptibility genes are also present and could modify the disease severity. All coding exons of SCN1B, GABRG2, and CACNB4 genes were screened for mutations in 38 SCN1A-mutation-positive SMEI probands. We identified one proband who was heterozygous for a de novo SCN1A nonsense mutation (R568X) and another missense mutation (R468Q) of the CACNB4 gene. The latter mutation was inherited from his father who had a history of febrile seizures. An electrophysiological analysis of heterologous expression system exhibited that R468Q-CACNB4 showed greater Ba(2+) current density compared with the wild-type CACNB4. The greater Ca(v)2.1 currents caused by the R468Q-CACNB4 mutation may increase the neurotransmitter release in the excitatory neurons under the condition of insufficient inhibitory neurons caused primarily by the SCN1A mutation.
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PMID:A CACNB4 mutation shows that altered Ca(v)2.1 function may be a genetic modifier of severe myoclonic epilepsy in infancy. 1875 74

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.
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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.
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PMID:Progress in searching for the febrile seizure susceptibility genes. 1920 61


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