Journal article

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies

Silke Appenzeller, Rudi Balling, Nina Barisic, Stephanie Baulac, Hande Caglayan, Dana Craiu, Peter De Jonghe, Christel Depienne, Petia Dimova, Tania Djemie, Padhraig Gormley, Renzo Guerrini, Ingo Helbig, Helle Hjalgrim, Dorota Hoffman-Zacharska, Johanna Jaehn, Karl Martin Klein, Bobby Koeleman, Vladimir Komarek, Roland Krause Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2014

Abstract

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large cohorts of well-characterized individuals to further define the genetic landscape. Through a collaboration between two consortia (EuroEPINOMICS and Epi4K/EPGP), we analyzed exome-sequencing data of 356 trios with the "classical" epileptic encephalopathies, infantile spasms and Lennox Gastaut syndrome, including 264 trios previously analyzed by the Epi4K/EPGP consortium. In this expanded cohort, we find 429 de novo mutations, including de novo mutations in DNM1 in five individuals and de novo mutations in GABBR2, FASN, and RYR3 in two individuals each. Unlike previ..

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Grants

Awarded by National Institute of Neurological Disorders and Stroke (The Epilepsy Phenome/Genome Project)


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

This work was supported by grants from the National Institute of Neurological Disorders and Stroke (The Epilepsy Phenome/Genome Project NS053998; Epi4K NS077364, NS077274, NS077303, and NS077276), The Andrew's Foundation, Finding a Cure for Epilepsy and Seizures, the Richard Thalheimer Philanthropic Fund, and the Eurocores program EuroEPINOMICS-RES of the European Science Foundation. Additional funding sources are summarized in the Supplemental Acknowledgments. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.