Re-annotation of 191 developmental and epileptic encephalopathy-associated genes unmasks de novo variants in SCN1A.

ABSTRACT: The developmental and epileptic encephalopathies (DEE) are a group of rare, severe neurodevelopmental disorders, where even the most thorough sequencing studies leave 60-65% of patients without a molecular diagnosis. Here, we explore the incompleteness of transcript models used for exome and genome analysis as one potential explanation for a lack of current diagnoses. Therefore, we have updated the GENCODE gene annotation for 191 epilepsy-associated genes, using human brain-derived transcriptomic libraries and other data to build 3,550 putative transcript models. Our annotations increase the transcriptional 'footprint' of these genes by over 674 kb. Using SCN1A as a case study, due to its close phenotype/genotype correlation with Dravet syndrome, we screened 122 people with Dravet s

SUBMITTER: Steward CA 

PROVIDER: S-EPMC6889285 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature