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https://hdl.handle.net/2440/11490
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Type: | Journal article |
Title: | Febrile seizures and generalised epilepsy associated with a mutation in the Na+-channel b1 subunit gene SCN1B |
Author: | Wallace, R. Wang, D. Singh, R. Scheffer, I. George Jnr., A. Phillips, H. Saar, K. Reis, A. Johnson, E. Sutherland, G. Berkovic, S. Mulley, J. |
Citation: | Nature Genetics, 1998; 19(4):366-370 |
Publisher: | Nature |
Issue Date: | 1998 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Robyn H. Wallace, Dao W. Wang, Rita Singh, Ingrid E. Scheffer, Alfred L. George, Jr., Hilary A. Phillips, Kathrin Saar, Andre Reis, Eric W. Johnson, Grant R. Sutherland, Samuel F. Berkovic & John C. Mulley |
Abstract: | 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. |
Keywords: | Oocytes Chromosomes, Human, Pair 19 Animals Xenopus laevis Humans Epilepsy, Generalized Seizures, Febrile Sodium Channels Patch-Clamp Techniques Pedigree DNA Mutational Analysis Amino Acid Sequence Point Mutation Molecular Sequence Data Tasmania Female Male Genetic Linkage |
Description: | Copyright © 1998 Nature America Inc. |
DOI: | 10.1038/1252 |
Published version: | http://dx.doi.org/10.1038/1252 |
Appears in Collections: | Aurora harvest 2 Genetics publications |
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