The role of recessive inheritance in early-onset epileptic encephalopathies: a combined whole-exome sequencing and copy number study.

ABSTRACT: Early-onset epileptic encephalopathy (EE) and combined developmental and epileptic encephalopathies (DEE) are clinically and genetically heterogeneous severely devastating conditions. Recent studies emphasized de novo variants as major underlying cause suggesting a generally low-recurrence risk. In order to better understand the full genetic landscape of EE and DEE, we performed high-resolution chromosomal microarray analysis in combination with whole-exome sequencing in 63 deeply phenotyped independent patients. After bioinformatic filtering for rare variants, diagnostic yield was improved for recessive disorders by manual data curation as well as molecular modeling of missense variants and untargeted plasma-metabolomics in selected patients. In total, we yielded a diagnosis in ∼42% of ca

SUBMITTER: Papuc SM 

PROVIDER: S-EPMC6460568 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature