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

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 genes, defining a genetic etiology in 3.2% of this unsolved cohort. Our results provide definitive

SUBMITTER: Epi4K Consortium 

PROVIDER: S-EPMC4974067 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature