Mutations in DEPDC5 cause familial focal epilepsy with variable foci

Leanne M. Dibbens, Boukje De Vries, Simona Donatello, Sarah E. Heron, Bree L. Hodgson, Satyan Chintawar, Douglas E. Crompton, James N. Hughes, Susannah T. Bellows, Karl Martin Klein, Petra M C Callenbach, Mark A. Corbett, Alison E. Gardner, Sara Kivity, Xenia Iona, Brigid M. Regan, Claudia M. Weller, Denis Crimmins, Terence J. O'Brien, Rosa Guerrero-LópezJohn C. Mulley, Francois Dubeau, Laura Licchetta, Francesca Bisulli, Patrick Cossette, Paul Q. Thomas, Jozef Gecz, Jose Serratosa, Oebele F Brouwer, Frederick Andermann, Eva Andermann, Arn M J M Van Den Maagdenberg, Massimo Pandolfo, Samuel F. Berkovic, Ingrid E. Scheffer

Research output: Contribution to journalArticlepeer-review

Abstract

The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors are increasingly recognized. Autosomal dominant familial focal epilepsy with variable foci (FFEVF) is notable because family members have seizures originating from different cortical regions. Using exome sequencing, we detected DEPDC5 mutations in two affected families. We subsequently identified mutations in five of six additional published large families with FFEVF. Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families (10/82). This high frequency establishes DEPDC5 mutations as a common cause of familial focal epilepsies. Shared homology with G protein signaling molecules and localization in human neurons suggest a role of DEPDC5 in neuronal signal transduction.

Original languageEnglish
Pages (from-to)546-551
Number of pages6
JournalNature Genetics
Volume45
Issue number5
DOIs
Publication statusPublished - May 2013

ASJC Scopus subject areas

  • Genetics

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