Type

Journal Article

Authors

Mary D King
Sally A Lynch
Sean Ennis
Tiago R Magalhães
Dara McCreary
Sergio D J Pena
Raony G Correa
Bryan Lynch
Amre Shahwan
Judith Conroy
and 1 others

Subjects

Medicine & Nursing

Topics
brain phenotype children expansion approaches screening genes metabolism

Unexplained early onset epileptic encephalopathy: Exome screening and phenotype expansion. (2015)

Abstract Early onset epileptic encephalopathies (EOEEs) represent a significant diagnostic challenge. Newer genomic approaches have begun to elucidate an increasing number of responsible single genes as well as emerging diagnostic strategies. In this single-center study, we aimed to investigate a cohort of children with unexplained EOEE. We performed whole-exome sequencing (WES), targeting a list of 137 epilepsy-associated genes on 50 children with unexplained EOEE. We characterized all phenotypes in detail and classified children according to known electroclinical syndromes where possible. Infants with previous genetic diagnoses, causative brain malformations, or inborn errors of metabolism were excluded. We identified disease-causing variants in 11 children (22%) in the following genes: STXBP1 (n = 3), KCNB1 (n = 2), KCNT1, SCN1A, SCN2A, GRIN2A, DNM1, and KCNA2. We also identified two further variants (in GRIA3 and CPA6) in two children requiring further investigation. Eleven variants were de novo, and in one paternal testing was not possible. Phenotypes were broadened for some variants identified. This study demonstrates that WES is a clinically useful screening tool for previously investigated unexplained EOEE and allows for reanalysis of data as new genes are being discovered. Detailed phenotyping allows for expansion of specific gene disorders leading to epileptic encephalopathy and emerging sub-phenotypes.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Mary D King, Sally A Lynch, Sean Ennis, Tiago R Magalhães, Dara McCreary, Sergio D J Pena, Raony G Correa, Bryan Lynch, Amre Shahwan, Judith Conroy and 1 others

Experts in our system

1
Mary D King
University College Dublin
Total Publications: 27
 
2
Sally Ann Lynch
University College Dublin
Total Publications: 32
 
3
Sean Ennis
University College Dublin
Total Publications: 52
 
4
Bryan Lynch
University College Dublin
Total Publications: 3
 
5
Judith Conroy
University College Dublin
Total Publications: 24