Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009952 (febrile convulsions)
 1,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder. A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures. Segregation analysis suggests the majority of cases have complex inheritance but rare families show apparent autosomal dominant inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified. We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS+), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures. We now report linkage, in another large GEFS+ family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel beta1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Co-expression of the mutant beta1 subunit with a brain Na+-channel alpha subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.
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PMID:Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. 969 98

The syndrome of generalized epilepsy with febrile seizure plus (GEFS+) is associated with a single point mutation on the gene SCN1B that results in a substitution of the cysteine 121 with a tryptophane in the sodium channel beta 1-subunit protein. We have studied, in the HEK cells permanently transfected with the skeletal muscle sodium channel alpha-subunit (SkM1), the effects of a transient transfection of the wild type (WT) or C121W mutant beta 1-subunit. Coexpression of the WT beta 1 produces two effects on the sodium currents expressed in mammalian cells: the increase in the density of sodium channels, and the modulation of the inactivation of the sodium currents, inducing a hastening of the recovery from the inactivation. This modulation is less severe as observed when sodium channels are expressed in frog oocytes. We have observed that mutant C121W lacks this modulatory property, but maintains its property to increase the current density. Our observation suggests a possible involvement of this lack of modulation in the development of the GEFS+, providing the first hypothesis based on the observation of the functional properties of the beta 1-subunit C121W mutant in mammalian cells, which certainly represents a more physiological preparation, instead of in Xenopus oocytes, where the modulatory properties of the beta 1-subunit are artificially amplified.
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PMID:Modulation of sodium current in mammalian cells by an epilepsy-correlated beta 1-subunit mutation. 1186 77