Australian Researchers Discover Gene for Common Form of Focal Epilepsy

Researchers from the Florey Neuroscience Institute in Melbourne, Victoria, Australia along with an international team of colleagues have published their discovery of the focal epilepsy gene in 31 March online issue of Nature Genetics¹.

 

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, they detected mutations of the DEPDC5 gene in two affected families and 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.

 

According to lead researcher, Professor Ingrid Scheffer at the Florey Neuroscience Institute in Melbourne, Victoria, Australia, this discovery is paradigm shifting, opening up new opportunities for diagnosing epilepsy.In the families studied, the researchers noted there were some individuals with intellectual disabilities, and some with autism spectrum disorders and psychiatric features.It is possible DEPDC5 may well play a role in these other disorders too, but it is too early to establish such a causal connection without more detailed study of patients with these conditions and similar gene mutations. This work was supported by the National Health and Medical Research Council of Australia.

 

Professor Ingrid Scheffer will be organizing a symposium on "Advances in Genetics on Focal Epilepsies" at the 13th International Child Neurology Congress to held at Iguazu Falls, Brasil May 4-9 2014.

 

 

1.Dibbens LM, de Vries B, Donatello S, Heron SE, Hodgson BL, Chintawar S, Crompton DE, Hughes JN, Bellows ST, Klein KM, Callenbach PM, Corbett MA, Gardner AE, Kivity S, Iona X, Regan BM, Weller CM, Crimmins D, O'Brien TJ, Guerrero-López R, Mulley JC, Dubeau F, Licchetta L, Bisulli F, Cossette P, Thomas PQ, Gecz J, Serratosa J, Brouwer OF, Andermann F, Andermann E, van den Maagdenberg AM, Pandolfo M, Berkovic SF, Scheffer IE. Mutations in DEPDC5 cause familial focal epilepsy with variable foci. Nat Genet. 2013 Mar 31. doi: 10.1038/ng.2599. [Epub ahead of print] PubMed PMID: 23542697.