Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data.

Journal Article (Journal Article;Multicenter Study)

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure disorders that usually arise sporadically. De novo variants in genes mainly encoding ion channel and synaptic proteins have been found to account for over 15% of patients with IS or LGS. The contribution of autosomal recessive genetic variation, however, is less well understood. We implemented a rare variant transmission disequilibrium test (TDT) to search for autosomal recessive epileptic encephalopathy genes in a cohort of 320 outbred patient-parent trios that were generally prescreened for rare metabolic disorders. In the current sample, our rare variant transmission disequilibrium test did not identify individual genes with significantly distorted transmission over expectation after correcting for the multiple tests. While the rare variant transmission disequilibrium test did not find evidence of a role for individual autosomal recessive genes, our current sample is insufficiently powered to assess the overall role of autosomal recessive genotypes in an outbred epileptic encephalopathy population.

Full Text

Duke Authors

Cited Authors

  • Epi4K Consortium, ; EuroEPINOMICS-RES Consortium, ; Epilepsy Phenome Genome Project,

Published Date

  • June 2017

Published In

Volume / Issue

  • 25 / 7

Start / End Page

  • 894 - 899

PubMed ID

  • 28513609

Pubmed Central ID

  • PMC5520073

Electronic International Standard Serial Number (EISSN)

  • 1476-5438

Digital Object Identifier (DOI)

  • 10.1038/ejhg.2017.61


  • eng

Conference Location

  • England