title: Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.
abstract: BACKGROUND
  Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS+ in a significant proportion of patients with SMEI. Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy.
  
  
  METHODS
  The authors screened SCN1A in 24 patients with SMEI and 23 with IS.
  
  
  RESULTS
  Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI.
  
  
  CONCLUSIONS
  The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS+ could interact with other loci to cause SMEI in cases with a family history of GEFS+. This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001315:Australia; D002648:Child; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017434:Protein Structure, Tertiary; D022821:RNA Splice Sites / Q000235:genetics; D003294:Seizures, Febrile / Q000235:genetics; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics*; D013036:Spasms, Infantile / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D018389:Codon, Nonsense; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D022821:RNA Splice Sites; C568242:SCN1A protein, human; D015222:Sodium Channels