Recurrent De Novo Mutations of SCN1A in Severe Myoclonic Epilepsy of Infancy

Kearney, Jennifer A.; Wiste, Anna K.; Stephani, Ulrich; Trudeau, Michelle M.; Siegel, Anne; RamachandranNair, Rajesh; Elterman, Roy D.; Muhle, Hiltrud; Reinsdorf, Juliane; Shields, W. Donald; Meisler, Miriam H.; Escayg, Andrew

doi:10.1016/j.pediatrneurol.2005.07.009

« Previous Next »Pediatric Neurology
Volume 34, Issue 2 , Pages 116-120, February 2006

Recurrent De Novo Mutations of SCN1A in Severe Myoclonic Epilepsy of Infancy

Jennifer A. Kearney, PhD
- Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Anna K. Wiste, BS
- Department of Human Genetics, Emory University, Atlanta, Georgia
Ulrich Stephani, MD
- Neuropediatric Department, University Hospital Schlewig-Holstein, Campus Kiel, Kiel, Germany
Michelle M. Trudeau, MS
- Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Anne Siegel, BS
- Department of Human Genetics, Emory University, Atlanta, Georgia
Rajesh RamachandranNair, MD
- Department of Pediatrics, The Hospital for Sick Children, Toronto, Canada
Roy D. Elterman, MD
- Department of Pediatrics, University of Texas Southwestern Medical School at Dallas, Dallas, Texas
Hiltrud Muhle, MD
- Neuropediatric Department, University Hospital Schlewig-Holstein, Campus Kiel, Kiel, Germany
Juliane Reinsdorf, MD
- Neuropediatric Department, University Hospital Schlewig-Holstein, Campus Kiel, Kiel, Germany
W. Donald Shields, MD
- Department of Pediatrics, University of California at Los Angeles
Miriam H. Meisler, PhD
- Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
Andrew Escayg, PhD
- Department of Human Genetics, Emory University, Atlanta, Georgia
- Communications should be addressed to: Dr. Escayg; Department of Human Genetics; Emory University; 615 Michael Street; Whitehead Building, Suite 301; Atlanta, GA 30322.

Received 17 February 2005; accepted 21 July 2005.

Mutations in the voltage-gated sodium channel gene SCN1A are a major cause of severe myoclonic epilepsy of infancy (Dravet syndrome) and generalized epilepsy with febrile seizures plus. This study reports the identification of six de novo SCN1A mutations in patients with severe myoclonic epilepsy of infancy, including a tetranucleotide deletion in exon 26. The same deletion was previously observed in two unrelated patients and appears to result from slipped-strand mispairing of a direct repeat during deoxyribonucleic acid replication. Review of the literature indicates that recurrent mutations account for 25% of SCN1A mutations in severe myoclonic epilepsy of infancy, including six sites of deamination at CpG dinucleotides.