Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Allen, AS and Bellows, ST and Berkovic, SF and Bridgers, J and Burgess, R and Cavalleri, G and Chung, S-K and Cossette, P and Delanty, N and Dlugos, D and Epstein, MP and Freyer, C and Goldstein, DB and Heinzen, EL and Hildebrand, MS and Johnson, MR and Kuzniecky, R and Lowenstein, DH and Marson, AG and Mayeux, R and Mebane, C and Mefford, HC and O'Brien, TJ and Ottman, R and Petrou, S and Petrovski, S and Pickrell, WO and Poduri, A and Radtke, RA and Rees, MI and Regan, BM and Ren, Z and Scheffer, IE and Sills, GJ and Thomas, RH and Wang, Q and Abou-Khalil, B and Alldredge, BK and Amrom, D and Andermann, E and Andermann, F and Bautista, JF and Berkovic, SF and Bluvstein, J and Boro, A and Cascino, GD and Consalvo, D and Crumrine, P and Devinsky, O and Dlugos, D and Epstein, MP and Fiol, M and Fountain, NB and French, J and Freyer, C and Friedman, D and Geller, EB and Glauser, T and Glynn, S and Haas, K and Haut, SR and Hayward, J and Helmers, SL and Joshi, S and Kanner, A and Kirsch, },
doi = {10.1016/S1474-4422(16)30359-3},
journal = {The Lancet Neurology},
pages = {135--143},
title = {Ultra-rare genetic variation in common epilepsies: a case-control sequencing study},
url = {},
volume = {16},
year = {2017}

RIS format (EndNote, RefMan)

AB - BackgroundDespite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable to traditional gene-discovery analyses. We aimed to assess the contribution of ultra-rare genetic variation to common epilepsies.MethodsWe did a case-control sequencing study with exome sequence data from unrelated individuals clinically evaluated for one of the two most common epilepsy syndromes: familial genetic generalised epilepsy, or familial or sporadic non-acquired focal epilepsy. Individuals of any age were recruited between Nov 26, 2007, and Aug 2, 2013, through the multicentre Epilepsy Phenome/Genome Project and Epi4K collaborations, and samples were sequenced at the Institute for Genomic Medicine (New York, USA) between Feb 6, 2013, and Aug 18, 2015. To identify epilepsy risk signals, we tested all protein-coding genes for an excess of ultra-rare genetic variation among the cases, compared with control samples with no known epilepsy or epilepsy comorbidity sequenced through unrelated studies.FindingsWe separately compared the sequence data from 640 individuals with familial genetic generalised epilepsy and 525 individuals with familial non-acquired focal epilepsy to the same group of 3877 controls, and found significantly higher rates of ultra-rare deleterious variation in genes established as causative for dominant epilepsy disorders (familial genetic generalised epilepsy: odd ratio [OR] 2·3, 95% CI 1·7–3·2, p=9·1×10−8; familial non-acquired focal epilepsy 3·6, 2·7–4·9, p=1·1×10−17). Comparison of an additional cohort of 662 individuals with sporadic non-acquired focal epilepsy to controls did not identify study-wide significant signals. For the individuals with familial non-acquired focal epilepsy, we found that five known epilepsy genes ranked as the top five genes enriched for ultra-rare deleterious variation. After accounting fo
AU - Allen,AS
AU - Bellows,ST
AU - Berkovic,SF
AU - Bridgers,J
AU - Burgess,R
AU - Cavalleri,G
AU - Chung,S-K
AU - Cossette,P
AU - Delanty,N
AU - Dlugos,D
AU - Epstein,MP
AU - Freyer,C
AU - Goldstein,DB
AU - Heinzen,EL
AU - Hildebrand,MS
AU - Johnson,MR
AU - Kuzniecky,R
AU - Lowenstein,DH
AU - Marson,AG
AU - Mayeux,R
AU - Mebane,C
AU - Mefford,HC
AU - O'Brien,TJ
AU - Ottman,R
AU - Petrou,S
AU - Petrovski,S
AU - Pickrell,WO
AU - Poduri,A
AU - Radtke,RA
AU - Rees,MI
AU - Regan,BM
AU - Ren,Z
AU - Scheffer,IE
AU - Sills,GJ
AU - Thomas,RH
AU - Wang,Q
AU - Abou-Khalil,B
AU - Alldredge,BK
AU - Amrom,D
AU - Andermann,E
AU - Andermann,F
AU - Bautista,JF
AU - Berkovic,SF
AU - Bluvstein,J
AU - Boro,A
AU - Cascino,GD
AU - Consalvo,D
AU - Crumrine,P
AU - Devinsky,O
AU - Dlugos,D
AU - Epstein,MP
AU - Fiol,M
AU - Fountain,NB
AU - French,J
AU - Freyer,C
AU - Friedman,D
AU - Geller,EB
AU - Glauser,T
AU - Glynn,S
AU - Haas,K
AU - Haut,SR
AU - Hayward,J
AU - Helmers,SL
AU - Joshi,S
AU - Kanner,A
AU - Kirsch,HE
AU - Knowlton,RC
AU - Kossoff,EH
AU - Kuperman,R
AU - Kuzniecky,R
AU - Lowenstein,DH
AU - Motika,PV
AU - Novotny,EJ
AU - Ottman,R
AU - Paolicchi,JM
AU - Parent,JM
AU - Park,K
AU - Poduri,A
AU - Sadleir,LG
AU - Scheffer,IE
AU - Shellhaas,RA
AU - Sherr,EH
AU - Shih,JJ
AU - Shinnar,S
AU - Singh,RK
AU - Sirven,J
AU - Smith,MC
AU - Sullivan,J
AU - Thio,LL
AU - Venkat,A
AU - Vining,EPG
AU - Von,Allmen GK
AU - Weisenberg,JL
AU - Widdess-Walsh,P
AU - Winawer,MR
DO - 10.1016/S1474-4422(16)30359-3
EP - 143
PY - 2017///
SN - 1474-4422
SP - 135
TI - Ultra-rare genetic variation in common epilepsies: a case-control sequencing study
T2 - The Lancet Neurology
UR -
UR -
VL - 16
ER -