Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {May, P and Girard, S and Harrer, M and Bobbili, DR and Schubert, J and Wolking, S and Becker, F and Lachance-Touchette, P and Meloche, C and Gravel, M and Niturad, CE and Knaus, J and De, Kovel C and Toliat, M and Polvi, A and Iacomino, M and Guerrero-Lopez, R and Baulac, S and Marini, C and Thiele, H and Altmueller, J and Jabbari, K and Ruppert, A-K and Jurkowski, W and Lal, D and Rusconi, R and Cestele, S and Terragni, B and Coombs, ID and Reid, CA and Striano, P and Caglayan, H and Siren, A and Everett, K and Moller, RS and Hjalgrim, H and Muhle, H and Helbig, I and Kunz, WS and Weber, YG and Weckhuysen, S and De, Jonghe P and Sisodiya, SM and Nabbout, R and Franceschetti, S and Coppola, A and Vari, MS and Trenite, DK-N and Baykan, B and Ozbek, U and Bebek, N and Klein, KM and Rosenow, F and Nguyen, DK and Dubeau, F and Carmant, L and Lortie, A and Desbiens, R and Clement, J-F and Cieuta-Walti, C and Sills, GJ and Auce, P and Francis, B and Johnson, MR and Marson, AG and Berghuis, B},
doi = {10.1016/S1474-4422(18)30215-1},
journal = {Lancet Neurology},
pages = {699--708},
title = {Rare coding variants in genes encoding GABA(A) receptors in genetic generalised epilepsies: an exome-based case-control study},
url = {},
volume = {17},
year = {2018}

RIS format (EndNote, RefMan)

AB - BackgroundGenetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.MethodsFor this exome-based case-control study, we used three different genetic generalised epilepsy case cohorts and three independent control cohorts, all of European descent. Cases included in the study were clinically evaluated for genetic generalised epilepsy. Whole-exome sequencing was done for the discovery case cohort, a validation case cohort, and two independent control cohorts. The replication case cohort underwent targeted next-generation sequencing of the 19 known genes encoding subunits of GABAA receptors and was compared to the respective GABAA receptor variants of a third independent control cohort. Functional investigations were done with automated two-microelectrode voltage clamping in Xenopus laevis oocytes.FindingsStatistical comparison of 152 familial index cases with genetic generalised epilepsy in the discovery cohort to 549 ethnically matched controls suggested an enrichment of rare missense (Nonsyn) variants in the ensemble of 19 genes encoding GABAA receptors in cases (odds ratio [OR] 2·40 [95% CI 1·41–4·10]; pNonsyn=0·0014, adjusted pNonsyn=0·019). Enrichment for these genes was validated in a whole-exome sequencing cohort of 357 sporadic and familial genetic generalised epilepsy cases and 1485 independent controls (OR 1·46 [95% CI 1·05–2·03]; pNonsyn=0·0081, adjusted pNonsyn=0·016). Comparison of genes encoding GABAA receptors in the independent replication cohort of 583 familial and sporadic genetic generalised epilepsy index cases, based on candidate-gene panel sequencing, with a third independent control cohort of 635 controls confirmed the overall enrichment of rare mis
AU - May,P
AU - Girard,S
AU - Harrer,M
AU - Bobbili,DR
AU - Schubert,J
AU - Wolking,S
AU - Becker,F
AU - Lachance-Touchette,P
AU - Meloche,C
AU - Gravel,M
AU - Niturad,CE
AU - Knaus,J
AU - De,Kovel C
AU - Toliat,M
AU - Polvi,A
AU - Iacomino,M
AU - Guerrero-Lopez,R
AU - Baulac,S
AU - Marini,C
AU - Thiele,H
AU - Altmueller,J
AU - Jabbari,K
AU - Ruppert,A-K
AU - Jurkowski,W
AU - Lal,D
AU - Rusconi,R
AU - Cestele,S
AU - Terragni,B
AU - Coombs,ID
AU - Reid,CA
AU - Striano,P
AU - Caglayan,H
AU - Siren,A
AU - Everett,K
AU - Moller,RS
AU - Hjalgrim,H
AU - Muhle,H
AU - Helbig,I
AU - Kunz,WS
AU - Weber,YG
AU - Weckhuysen,S
AU - De,Jonghe P
AU - Sisodiya,SM
AU - Nabbout,R
AU - Franceschetti,S
AU - Coppola,A
AU - Vari,MS
AU - Trenite,DK-N
AU - Baykan,B
AU - Ozbek,U
AU - Bebek,N
AU - Klein,KM
AU - Rosenow,F
AU - Nguyen,DK
AU - Dubeau,F
AU - Carmant,L
AU - Lortie,A
AU - Desbiens,R
AU - Clement,J-F
AU - Cieuta-Walti,C
AU - Sills,GJ
AU - Auce,P
AU - Francis,B
AU - Johnson,MR
AU - Marson,AG
AU - Berghuis,B
AU - Sander,JW
AU - Avbersek,A
AU - McCormack,M
AU - Cavalleri,GL
AU - Delanty,N
AU - Depondt,C
AU - Krenn,M
AU - Zimprich,F
AU - Peter,S
AU - Nikanorova,M
AU - Kraaij,R
AU - van,Rooij J
AU - Balling,R
AU - Ikram,MA
AU - Uitterlinden,AG
AU - Avanzini,G
AU - Schorge,S
AU - Petrou,S
AU - Mantegazza,M
AU - Sander,T
AU - LeGuern,E
AU - Serratosa,JM
AU - Koeleman,BPC
AU - Palotie,A
AU - Lehesjoki,A-E
AU - Nothnagel,M
AU - Nuernberg,P
AU - Maljevic,S
AU - Zara,F
AU - Cossette,P
AU - Krause,R
AU - Lerche,H
DO - 10.1016/S1474-4422(18)30215-1
EP - 708
PY - 2018///
SN - 1474-4422
SP - 699
TI - Rare coding variants in genes encoding GABA(A) receptors in genetic generalised epilepsies: an exome-based case-control study
T2 - Lancet Neurology
UR -
UR -
UR -
VL - 17
ER -