title: Novel de novo mutation of a conserved SCN1A amino-acid residue (R1596).
abstract: We report on the case of a 6-year-old boy with epilepsy involving febrile seizures and unprovoked generalized tonic clonic seizures. Genetic testing revealed a novel de novo mutation in the SCN1A gene (C>T 4786, R1596C). The epilepsy phenotype is within the spectrum of generalized epilepsy with febrile seizures plus. However, de novo mutations are more commonly reported in cases of severe myoclonic epilepsy of infancy, and are less often reported in generalized epilepsy with febrile seizures plus. The clinical utility of specific genetic testing in this case is discussed, as are criteria for determining the pathologic significance of novel DNA variants. In this case, the wild type of residue (R1596) is well-conserved across evolution from bacteria to humans, providing support for the hypothesis that this mutation causes epilepsy.
authors: Department of Neurology, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. dlugos@email.chop.edu
authors: Dennis J
authors: DJ
authors: Dlugos
authors: Thomas N
authors: TN
authors: Ferraro
authors: Russell J
authors: RJ
authors: Buono
mesh_terms: D001120:Arginine; D002648:Child; D017124:Conserved Sequence; D003545:Cysteine; D004829:Epilepsy, Generalized / Q000235:genetics*; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008297:Male; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; 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; D001120:Arginine; D003545:Cysteine