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%.
Wallace
R H
RH
The Bionomics/Women's and Children's Hospital Research Facility, Thebarton, South Australia, Australia, 5031. rwallace@wch.bionomics.com.au
Scheffer
I E
IE
Barnett
S
S
Richards
M
M
Dibbens
L
L
Desai
R R
RR
Lerman-Sagie
T
T
Lev
D
D
Mazarib
A
A
Brand
N
N
Ben-Zeev
B
B
Goikhman
I
I
Singh
R
R
Kremmidiotis
G
G
Gardner
A
A
Sutherland
G R
GR
George
A L
AL
Mulley
J C
JC
Berkovic
S F
SF
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