title: Clinical spectrum of SCN1A mutations.
abstract: Mutations in the NaV1.1 neuronal sodium channel alpha-subunit (SCN1A) gene have been documented in a spectrum of epilepsy syndromes, ranging from the relatively benign generalized epilepsy with febrile seizures plus (GEFS(+)) to severe myoclonic epilepsy in infancy (SMEI), and rare cases of familial migraine. More than 300 new mutations have been identified to date, with missense mutations being the most common in GEFS(+) and more deleterious mutations (nonsense, frameshift) representing the majority of SMEI mutations. Microchromosomal abnormalities including SCN1A deletions, amplifications, and duplications are also found in patients with SMEI. Deletions range in size from one single exon to abnormalities extending beyond SCN1A and involving contiguous genes. The majority of SCN1A mutations in SMEI arise de novo. SCN1A mutations are found throughout the protein structure, and some clustering of mutations is observed in the C-terminus and the loops between segments 5 and 6 of the first three domains of the protein. Functional studies so far show no consistent relationship between changes to channel properties and clinical phenotype.
authors.affiliation: Institute of Neurology, University Magna Graecia, Catanzaro, Italy. a.gambardella@isn.cnr.it
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambardella
authors.forename: Carla
authors.initials: C
authors.lastname: Marini
mesh_terms: D002648:Child; D004252:DNA Mutational Analysis; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels