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

作者：Allen Andrew S^*; Berkovic Samuel F; Bridgers Joshua; Cossette Patrick; Dlugos Dennis; Epstein Michael P; Glauser Tracy; Goldstein David B; Heinzen Erin L; Jiang Yu; Johnson Michael R; Kuzniecky Ruben; Lowenstein Daniel H; Marson Anthony G; Mefford Heather C; O'Brien Terence J; Ottman Ruth; Petrou Steven; Petrovski Slave; Poduri Annapurna; Ren Zhong; Scheffer Ingrid E; Sherr Elliott; Wang Quanli; Balling Rudi; Barisic Nina; Baulac Stephanie; Caglayan Hande; Craiu Dana; De Jonghe Peter

来源：European Journal of Human Genetics, 2017, 25(7): 894-899.

DOI：10.1038/ejhg.2017.61

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.

• 出版日期2017-6