Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus.
Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome characterized by the presence of febrile and afebrile seizures. The first gene, GEFS1, was mapped to chromosome 19q and was identified as the sodium-channel beta1-subunit, SCN1B. A second locus on chromosome 2q, GEFS2, was recently identified as the sodium-channel alpha1-subunit, SCN1A. Single-stranded conformation analysis (SSCA) of SCN1A was performed in 53 unrelated index cases to estimate the frequency of mutations in patients with GEFS+. No mutations were found in 17 isolated cases of GEFS+. Three novel SCN1A mutations-D188V, V1353L, and I1656M-were found in 36 familial cases; of the remaining 33 families, 3 had mutations in SCN1B. On the basis of SSCA, the combined frequency of SCN1A and SCN1B mutations in familial cases of GEFS+ was found to be 17%.
The Bionomics/Women's and Children's Hospital Research Facility, Thebarton, South Australia, Australia, 5031. rwallace@wch.bionomics.com.au
R H
RH
Wallace
I E
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Scheffer
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S
Barnett
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M
Richards
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L
Dibbens
R R
RR
Desai
T
T
Lerman-Sagie
D
D
Lev
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A
Mazarib
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N
Brand
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B
Ben-Zeev
I
I
Goikhman
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R
Singh
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Kremmidiotis
A
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Gardner
G R
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Sutherland
A L
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George
J C
JC
Mulley
S F
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Berkovic
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D021122:Protein Subunits; D003294:Seizures, Febrile / Q000235:genetics*; D016415:Sequence Alignment; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome
D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D021122:Protein Subunits; C568242:SCN1A protein, human; D015222:Sodium Channels