Journal article

De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

Candace T Myers, Jacinta M McMahon, Amy L Schneider, Slave Petrovski, Andrew S Allen, Gemma L Carvill, Matthew Zemel, Julia E Say-Kally, Amy J LaCroix, Erin L Heinzen, Georgina Hollingsworth, Marina Nikanorova, Mark Corbett, Jozef Gecz, David Coman, Jeremy Freeman, Sophie Calvert, Deepak Gill, Patrick Carney, Tally Lerman-Sagie Show all

AMERICAN JOURNAL OF HUMAN GENETICS | CELL PRESS | Published : 2016

Abstract

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequencing has highlighted the crucial contribution of de novo mutations to the genetic architecture of EEs as well as to their underlying genetic heterogeneity. Our previous whole-exome sequencing study of 264 parent-child trios revealed more than 290 candidate genes in which only a single individual had a de novo variant. We sought to identify additional pathogenic variants in a subset (n = 27) of these genes via targeted sequencing in an unsolved cohort of 531 individuals with a diverse range of EEs. We report 17 individuals with pathogenic variants in seven of the 27..

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Grants

Awarded by NIH National Institute of Neurological Disorders and Stroke Center without Walls


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

Funding for this study comes from the NIH National Institute of Neurological Disorders and Stroke Center without Walls (U01NS077274, U01NS077276, U01NS077303, U01NS077364, and U01NS077275 to the Epi4K administrative core and 2R01NS069605 to H.C.M.). David Goldstein, Steve Petrou, and Slave Petrovski have interests in companies related to epilepsy precision medicine.