Communicated by Arupa Ganguly
Mutations in Brief
Article first published online: 15 MAR 2006
© 2006 Wiley-Liss, Inc.
Volume 27, Issue 4, page 389, April 2006
How to Cite
Depienne, C., Arzimanoglou, A., Trouillard, O., Fedirko, E., Baulac, S., Saint-Martin, C., Ruberg, M., Dravet, C., Nabbout, R., Baulac, M., Gourfinkel-An, I. and Leguern, E. (2006), Parental mosaicism can cause recurrent transmission of SCN1A mutations associated with severe myoclonic epilepsy of infancy. Hum. Mutat., 27: 389. doi: 10.1002/humu.9419
Online Citation: Human Mutation, Mutation in Brief #890 (2006) Onlinehttp://www3.interscience.wiley.com/homepages/38515/pdf/890.pdf
- Issue published online: 15 MAR 2006
- Article first published online: 15 MAR 2006
- Manuscript Accepted: 23 FEB 2006
- Manuscript Received: 1 DEC 2005
- Cited By
- severe myoclonic epilepsy of infancy;
- Dravet syndrome;
De novo mutations in the SCN1A gene, encoding the alpha1-subunit of the neuronal voltage-gated sodium channel Nav1.1, are the most frequent genetic cause of Severe Myoclonic Epilepsy of Infancy known so far. A few mutations inherited from an asymptomatic or mildly affected parent have been reported, suggesting that expression of the mutated gene may be variable in the transmitting parent. In this study, we report two unrelated families in which two children of unaffected parents had deleterious SCN1A mutations, and show evidence of somatic and germline mosaicism in the transmitting parents. In one of these families, direct sequencing of blood cell DNA was not sufficient to the SCN1A mutation in the transmitting asymptomatic parent who was mosaic for the mutation. We therefore developed a real-time PCR assay to selectively amplify and quantify the mutant allele present at low levels in the transmitting parent in both families. The allele-specific PCR technique used in this study will be of use in detecting other such cases. These findings will have major consequences for the genetic counseling of asymptomatic parents with only one affected child. © 2006 Wiley-Liss, Inc.