title: Timing of de novo mutagenesis--a twin study of sodium-channel mutations.
abstract: De novo mutations are a cause of sporadic disease, but little is known about the developmental timing of such mutations. We studied concordant and discordant monozygous twins with de novo mutations in the sodium channel α1 subunit gene (SCN1A) causing Dravet's syndrome, a severe epileptic encephalopathy. On the basis of our findings and the literature on mosaic cases, we conclude that de novo mutations in SCN1A may occur at any time, from the premorula stage of the embryo (causing disease in the subject) to adulthood (with mutations in the germ-line cells of parents causing disease in offspring).
authors.affiliation: Epilepsy Research Center, Austin Health, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Lata
authors.initials: L
authors.lastname: Vadlamudi
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Dibbens
authors.forename: Kate M
authors.initials: KM
authors.lastname: Lawrence
authors.forename: Xenia
authors.initials: X
authors.lastname: Iona
authors.forename: Jacinta M
authors.initials: JM
authors.lastname: McMahon
authors.forename: Wayne
authors.initials: W
authors.lastname: Murrell
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D000328:Adult; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D005819:Genetic Markers; D018095:Germ-Line Mutation; D006801:Humans; D007223:Infant; D016296:Mutagenesis; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics*; D013997:Time Factors; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels