Timing of de novo mutagenesis--a twin study of sodium-channel mutations.

2010-09-30

Vadlamudi, Lata

Dibbens, Leanne M

Lawrence, Kate M

Iona, Xenia

McMahon, Jacinta M

Murrell, Wayne

Mackay-Sim, Alan

Scheffer, Ingrid E

Berkovic, Samuel F

Journal Article

10.1056/NEJMoa0910752

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).

link

The New England Journal of Medicine; 363(14): 1335-40

The New England Journal of Medicine