title: A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree.
abstract: Generalized epilepsy with febrile seizures plus (GEFS+) is an inherited epileptic syndrome with a marked clinical and genetic heterogeneity. Here we report the molecular characterization of a large pedigree with a severe clinical form of GEFS+. Genetic linkage analysis implied the involvement of the FEB3 in the disease phenotype of this family (parametric two-point lod-score of 2.2). Sequencing of the SCN1A gene revealed a novel aspartic acid for glycine substitution at position 1742 of this sodium channel subunit. The amino-acid replacement lies in the pore-forming region of domain IV of SCN1A. Our observations are consistent with the genotype-phenotype correlation studies suggesting that mutations in the pore-forming loop of SCN1A can lead to a clinically more severe epileptic syndrome.
authors.affiliation: Grupo de Genetica Molecular, Facultad de Medicina, Universidad de Antioquia, Medellin-Colombia; The Galton Laboratory, University College London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Pineda-Trujillo
authors.forename: J
authors.initials: J
authors.lastname: Carrizosa
authors.forename: W
authors.initials: W
authors.lastname: Cornejo
authors.forename: W
authors.initials: W
authors.lastname: Arias
authors.forename: C
authors.initials: C
authors.lastname: Franco
authors.forename: D
authors.initials: D
authors.lastname: Cabrera
authors.forename: G
authors.initials: G
authors.lastname: Bedoya
authors.forename: A
authors.initials: A
authors.lastname: Ruíz-Linares
mesh_terms: D000328:Adult; D017668:Age of Onset; D019943:Amino Acid Substitution; D001224:Aspartic Acid / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000150:complications / Q000208:ethnology / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D005998:Glycine / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D003294:Seizures, Febrile / Q000150:complications / Q000208:ethnology / Q000235:genetics; D012720:Severity of Illness Index; D015222:Sodium Channels / Q000235:genetics*; D013020:South America
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels; D001224:Aspartic Acid; D005998:Glycine