Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {Andrew, S Allen1 and Samuel, F Berkovic2 and Patrick, Cossette3 and Norman, Delanty4 and Dennis, Dlugos5 and Evan, E Eichler6 and Michael, P Epstein7 and Tracy, Glauser8 and David, B Goldstein9 and Johnson, MR and Ruben, Kuzniecky12 and Daniel, H Lowenstein13 and Yi-Fan, Lu9 and Maura, R ZMadou and Anthony, G Marson14 and Heather, C Mefford15 and Sahar, Esmaeeli Nieh16 and Terence, J OBrien17 and Ruth, Ottman18 and Slave, Petrovski2 9 17 and Annapurna, Poduri19 and Elizabeth, K Ruzzo9 and Ingrid, E Scheffer20 21 and Elliott, H Sherr22 & Christopher J Yuskaitis23 and Bassel, Abou-Khalil24 and Brian, K Alldredge25 and Jocelyn, F Bautista26 and Samuel, F Berkovic2 and Alex, Boro27 and Gregory, D Cascino28 and Damian, Consalvo29 and Patricia, Crumrine30 and Orinn, Devinsky31 and Dennis, Dlugos5 and Michael, P Epstein7 and Miguel, Fiol32 and Nathan, B Fountain33 and Jacqueline, French12 and Daniel, Friedman12 and Eric, B Geller34 and Tracy, Glauser8 and sIMON, Glynn35 and Sheryl, R Haut36 a},
doi = {10.1038/nature12439},
journal = {Nature},
pages = {217--221},
title = {De novo mutations in epileptic encephalopathies},
url = {},
volume = {501},
year = {2013}

RIS format (EndNote, RefMan)

AB - Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown1. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox–Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10−3). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10−10 and P = 7.8 × 10−12, respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10−8), as has been reported previously for autism spectrum disorders2.
AU - Andrew,S Allen1
AU - Samuel,F Berkovic2
AU - Patrick,Cossette3
AU - Norman,Delanty4
AU - Dennis,Dlugos5
AU - Evan,E Eichler6
AU - Michael,P Epstein7
AU - Tracy,Glauser8
AU - David,B Goldstein9
AU - Johnson,MR
AU - Ruben,Kuzniecky12
AU - Daniel,H Lowenstein13
AU - Yi-Fan,Lu9
AU - Maura,R ZMadou
AU - Anthony,G Marson14
AU - Heather,C Mefford15
AU - Sahar,Esmaeeli Nieh16
AU - Terence,J OBrien17
AU - Ruth,Ottman18
AU - Slave,Petrovski2 9 17
AU - Annapurna,Poduri19
AU - Elizabeth,K Ruzzo9
AU - Ingrid,E Scheffer20 21
AU - Elliott,H Sherr22 & Christopher J Yuskaitis23
AU - Bassel,Abou-Khalil24
AU - Brian,K Alldredge25
AU - Jocelyn,F Bautista26
AU - Samuel,F Berkovic2
AU - Alex,Boro27
AU - Gregory,D Cascino28
AU - Damian,Consalvo29
AU - Patricia,Crumrine30
AU - Orinn,Devinsky31
AU - Dennis,Dlugos5
AU - Michael,P Epstein7
AU - Miguel,Fiol32
AU - Nathan,B Fountain33
AU - Jacqueline,French12
AU - Daniel,Friedman12
AU - Eric,B Geller34
AU - Tracy,Glauser8
AU - sIMON,Glynn35
AU - Sheryl,R Haut36
AU - Jean,Hayward37
AU - Sandra,L Helmers38
AU - Sucheta,Joshi39
AU - Andres,Kanner40
AU - Heidi,E Kirsch13 41
AU - Robert,C Knowlton42
AU - Eric,H Kossoff43
AU - Rachel,Kuperman44
AU - Ruben,Kuzniecky12
AU - Daniel,H Lowenstein13
AU - Shannon,M McGuire45
AU - Paul,V Motika46
AU - Edward,J Novotny47
AU - Ruth,Ottman18
AU - Juliann,M Paolicchi48
AU - Jack,Parent49 50
AU - Kristen,Park51
AU - Annapurna,Poduri19
AU - Ingrid,E Scheffer20 21
AU - Renee,A Shellhaas52
AU - Elliott,H Sherr22
AU - Jerry,J Shih53
AU - Rani,Singh54
AU - Joseph,Sirven55
AU - Michael,C Smith40
AU - Joseph,Sullivan13
AU - K,Liu Lin Thio56
AU - Anu,Venkat5
AU - Eileen,P G Vining57
AU - GretchenK,VonAllmen58
AU - Judith,LWeisenberg59
AU - Peter,Widdess-Walsh34&Melodie RWinawer
DO - 10.1038/nature12439
EP - 221
PY - 2013///
SN - 0028-0836
SP - 217
TI - De novo mutations in epileptic encephalopathies
T2 - Nature
UR -
UR -
VL - 501
ER -