Timing of de novo mutagenesis--a twin study of sodium-channel mutations.
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).
Vadlamudi
Lata
L
Epilepsy Research Center, Austin Health, University of Melbourne, Melbourne, VIC, Australia.
Dibbens
Leanne M
LM
Lawrence
Kate M
KM
Iona
Xenia
X
McMahon
Jacinta M
JM
Murrell
Wayne
W
Mackay-Sim
Alan
A
Scheffer
Ingrid E
IE
Berkovic
Samuel F
SF
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*
D005819:Genetic Markers; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels