Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus

Am J Hum Genet. 2001 Apr;68(4):859-65. doi: 10.1086/319516. Epub 2001 Mar 13.


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%.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Chromosomes, Human, Pair 2 / genetics
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Epilepsy, Generalized / genetics*
  • Exons / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Variation / genetics
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation / genetics*
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Protein Subunits
  • Seizures, Febrile / genetics*
  • Sequence Alignment
  • Sodium Channels / genetics*
  • Syndrome


  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Protein Subunits
  • SCN1A protein, human
  • Sodium Channels

Associated data

  • GENBANK/M22253
  • GENBANK/X65362