3 of 7 Epi4K: Gene Discovery in 4,000 Epilepsy Genomes

The role of copy number variants in the genetic architecture of common familial epilepsies

EP Almanza Fuerte, J Nguyen, M Mehaffey, A Sulovari, T Wang, M Galey, DE Miller, EE Eichler, HC Mefford, B Abou-Khalil, ZA Afawi, AS Allen, D Amrom, E Andermann, JF Bautista, ST Bellows, SF Berkovic, J Bluvstein, A Boro, R Burgess

2024-03-01

Objective: Copy number variants (CNVs) contribute to genetic risk and genetic etiology of both rare and common epilepsies. Whereas..

Association of ultra-rare coding variants with genetic generalized epilepsy: A case–control whole exome sequencing study

M Koko, JE Motelow, KE Stanley, DR Bobbili, RS Dhindsa, P May, BK Alldredge, AS Allen, J Altmüller, D Amrom, E Andermann, P Auce, A Avbersek, S Baulac, JF Bautista, F Becker, ST Bellows, B Berghuis, SF Berkovic, J Bluvstein

2022-03-01

Objective: We aimed to identify genes associated with genetic generalized epilepsy (GGE) by combining large cohorts enriched with ..

Diverse genetic causes of polymicrogyria with epilepsy

AS Allen, V Aggarwal, SF Berkovic, P Cossette, N Delanty, D Dlugos, EE Eichler, MP Epstein, C Freyer, DB Goldstein, R Guerrini, T Glauser, EL Heinzen, MR Johnson, R Kuzniecky, DH Lowenstein, AG Marson, HC Mefford, TJ O'Brien, R Ottman

2021-04-01

Objective: We sought to identify novel genes and to establish the contribution of known genes in a large cohort of patients with n..

A new approach for rare variation collapsing on functional protein domains implicates specific genic regions in ALS

S Gelfman, S Dugger, C de Araujo Martins Moreno, Z Ren, CJ Wolock, NA Shneider, H Phatnani, ET Cirulli, BN Lasseigne, T Harris, T Maniatis, GA Rouleau, RH Brown, AD Gitler, RM Myers, S Petrovski, A Allen, DB Goldstein, MB Harms

2019-05-01

Large-scale sequencing efforts in amyotrophic lateral sclerosis (ALS) have implicated novel genes using gene-based collapsing meth..

The Epilepsy Genetics Initiative: Systematic reanalysis of diagnostic exomes increases yield

SF Berkovic, DB Goldstein, EL Heinzen, BL Laughlin, DH Lowenstein, L Lubbers, R Stewart, V Whittemore, K Angione, CW Bazil, L Bier, J Bluvstein, E Brimble, C Campbell, G Cavalleri, C Chambers, H Choi, MR Cilio, M Ciliberto, S Cornes

2019-05-01

Objective: The E (EGI) was formed in 2014 to create a centrally managed database of clinically generated exome sequence data. EGI ..

Missense Variants in the Histone Acetyltransferase Complex Component Gene TRRAP Cause Autism and Syndromic Intellectual Disability

B Cogné, S Ehresmann, E Beauregard-Lacroix, J Rousseau, T Besnard, T Garcia, S Petrovski, S Avni, K McWalter, PR Blackburn, SJ Sanders, K Uguen, J Harris, JS Cohen, M Blyth, A Lehman, J Berg, MH Li, U Kini, S Joss

2019-03-07

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene ..

Whole-exome sequencing in 20,197 persons for rare variants in Alzheimer's disease

NS Raghavan, AM Brickman, H Andrews, JJ Manly, N Schupf, R Lantigua, CJ Wolock, S Kamalakaran, S Petrovski, G Tosto, BN Vardarajan, DB Goldstein, R Mayeux

2018-07-01

Objective: The genetic bases of Alzheimer's disease remain uncertain. An international effort to fully articulate genetic risks an..

De novo and inherited private variants in MAP1B in periventricular nodular heterotopia

EL Heinzen, AC O'Neill, X Zhu, AS Allen, M Bahlo, J Chelly, MH Chen, WB Dobyns, S Freytag, R Guerrini, RJ Leventer, A Poduri, SP Robertson, CA Walsh, M Zhang

2018-05-01

Periventricular nodular heterotopia (PVNH) is a malformation of cortical development commonly associated with epilepsy. We exome s..

De novo variants in the alternative exon 5 of SCN8A cause epileptic encephalopathy

SF Berkovic, B Grinton, T Dixon-Salazar, BL Laughlin, L Lubbers, J Milder, DB Goldstein, EL Heinzen, L Bier, ME Ernst, NC Lippa, MS Mulhern, TM Afgani, V Aggarwal, N Stong, DH Lowenstein, S Cornes, K Johnson, R Stewart, V Whittemore

2018-02-01

Purpose: As part of the Epilepsy Genetics Initiative, we reevaluated clinically generated exome sequence data from 54 epilepsy pat..

Annotating pathogenic non-coding variants in genic regions

S Gelfman, Q Wang, KM McSweeney, Z Ren, F La Carpia, M Halvorsen, K Schoch, F Ratzon, EL Heinzen, MJ Boland, S Petrovski, DB Goldstein

2017-12-01

Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively c..

A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations

X Zhu, R Padmanabhan, B Copeland, J Bridgers, Z Ren, S Kamalakaran, A O'Driscoll-Collins, SF Berkovic, IE Scheffer, A Poduri, D Mei, R Guerrini, DH Lowenstein, AS Allen, EL Heinzen, DB Goldstein

2017-11-01

Trio exome sequencing has been successful in identifying genes with de novo mutations (DNMs) causing epileptic encephalopathy (EE)..

De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures

CT Myers, N Stong, EI Mountier, KL Helbig, S Freytag, JE Sullivan, B Ben Zeev, A Nissenkorn, M Tzadok, G Heimer, DN Shinde, A Rezazadeh, BM Regan, KL Oliver, ME Ernst, NC Lippa, MS Mulhern, Z Ren, A Poduri, DM Andrade

2017-10-05

Exome sequencing has readily enabled the discovery of the genetic mutations responsible for a wide range of diseases. This success..

Orion: Detecting regions of the human noncoding genome that are intolerant to variation using population genetics

AB Gussow, BR Copeland, RS Dhindsa, Q Wang, S Petrovski, WH Majoros, AS Allen, DB Goldstein

2017-08-01

There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. ..

Phenotypic analysis of 303 multiplex families with common epilepsies

B Abou-Khalil, Z Afawi, AS Allen, JF Bautista, ST Bellows, SF Berkovic, J Bluvstein, R Burgess, G Cascino, EJ Cops, P Cossette, S Cristofaro, DE Crompton, N Delanty, O Devinsky, D Dlugos, MP Epstein, NB Fountain, C Freyer, SI Garry

2017-08-01

Gene identification in epilepsy has mainly been limited to large families segregating genes of major effect and de novo mutations ..

DNM1 encephalopathy

S Von Spiczak, KL Helbig, DN Shinde, R Huether, M Pendziwiat, C Lourenço, ME Nunes, DP Sarco, RA Kaplan, DJ Dlugos, H Kirsch, A Slavotinek, MR Cilio, MC Cervenka, JS Cohen, R McClellan, A Fatemi, A Yuen, Y Sagawa, R Littlejohn

2017-07-25

Objective: To evaluate the phenotypic spectrum caused by mutations in dynamin 1 (DNM1), encoding the presynaptic protein DNM1, and..

Application of rare variant transmission disequilibrium tests to epileptic encephalopathy trio sequence data

AS Allen, SF Berkovic, J Bridgers, P Cossette, D Dlugos, MP Epstein, T Glauser, DB Goldstein, EL Heinzen, Y Jiang, MR Johnson, R Kuzniecky, DH Lowenstein, AG Marson, HC Mefford, TJ O'Brien, R Ottman, S Petrou, S Petrovski, A Poduri

2017-06-01

The classic epileptic encephalopathies, including infantile spasms (IS) and Lennox-Gastaut syndrome (LGS), are severe seizure diso..

Ultra-rare genetic variation in common epilepsies: a case-control sequencing study

AS Allen, ST Bellows, SF Berkovic, J Bridgers, R Burgess, G Cavalleri, SK Chung, P Cossette, N Delanty, D Dlugos, MP Epstein, C Freyer, DB Goldstein, EL Heinzen, MS Hildebrand, MR Johnson, R Kuzniecky, DH Lowenstein, AG Marson, R Mayeux

2017-02-01

Background Despite progress in understanding the genetics of rare epilepsies, the more common epilepsies have proven less amenable..

De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies

CT Myers, JM McMahon, AL Schneider, S Petrovski, AS Allen, GL Carvill, M Zemel, JE Saykally, AJ LaCroix, EL Heinzen, G Hollingsworth, M Nikanorova, M Corbett, J Gecz, D Coman, J Freeman, S Calvert, D Gill, P Carney, T Lerman-Sagie

2016-08-04

Epileptic encephalopathies (EEs) are the most clinically important group of severe early-onset epilepsies. Next-generation sequenc..

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature

S Petrovski, RE Parrott, JL Roberts, H Huang, J Yang, B Gorentla, T Mousallem, E Wang, M Armstrong, D McHale, NJ MacIver, DB Goldstein, XP Zhong, RH Buckley

2016-07-01

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency..

Mosaic mutations in early-onset genetic diseases

M Halvorsen, S Petrovski, R Shellhaas, Y Tang, L Crandall, D Goldstein, O Devinsky

2016-07-01

Purpose:An emerging approach in medical genetics is to identify de novo mutations in patients with severe early-onset genetic dise..

The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes

AB Gussow, S Petrovski, Q Wang, AS Allen, DB Goldstein

2016-01-18

Ranking human genes based on their tolerance to functional genetic variation can greatly facilitate patient genome interpretation...

A roadmap for precision medicine in the epilepsies

SF Berkovic, IE Scheffer, S Petrou, N Delanty, TJ Dixon-Salazar, DJ Dlugos, I Helbig, WN Frankel, DB Goldstein, EL Heinzen, DH Lowenstein, HC Mefford, JM Parent, A Poduri, SF Traynelis

2015-12-01

Technological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view...

Whole-exome sequencing in undiagnosed genetic diseases: Interpreting 119 trios

X Zhu, S Petrovski, P Xie, EK Ruzzo, YF Lu, KM McSweeney, B Ben-Zeev, A Nissenkorn, Y Anikster, D Oz-Levi, RS Dhindsa, Y Hitomi, K Schoch, RC Spillmann, G Heimer, D Marek-Yagel, M Tzadok, Y Han, G Worley, J Goldstein

2015-10-01

Purpose:Despite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain ..

Incorporating Functional Information in Tests of Excess De Novo Mutational Load

Y Jiang, Y Han, S Petrovski, K Owzar, DB Goldstein, AS Allen

2015-08-06

A number of recent studies have investigated the role of de novo mutations in various neurodevelopmental and neuropsychiatric diso..

Copy number variant analysis from exome data in 349 patients with epileptic encephalopathy

Bassel Abou-Khalil, Brian K Alldredge, Andrew S Allen, Eva Andermann, Frederick Andermann, Dina Amrom, Jocelyn F Bautista, Samuel F Berkovic, Alex Boro, Gregory Cascino, Bradley P Coe, Damian Consalvo, Joseph Cook, Patrick Cossette, Patricia Crumrine, Norman Delanty, Orrin Devinsky, Dennis Dlugos, Evan E Eichler, Michael P Epstein

2015-08-01

Infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) are epileptic encephalopathies characterized by early onset, intractable s..

Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis

RS Dhindsa, SS Bradrick, X Yao, EL Heinzen, S Petrovski, BJ Krueger, MR Johnson, WN Frankel, S Petrou, RM Boumil, DB Goldstein

2015-06-01

Objective: To elucidate the functional consequences of epileptic encephalopathy-causing de novo mutations in DNM1 (A177P, K206N, G..

The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

S Petrovski, AB Gussow, Q Wang, M Halvorsen, Y Han, WH Weir, AS Allen, DB Goldstein

2015-01-01

Noncoding sequence contains pathogenic mutations. Yet, compared with mutations in protein-coding sequence, pathogenic regulatory m..

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

S Appenzeller, R Balling, N Barisic, S Baulac, H Caglayan, D Craiu, P De Jonghe, C Depienne, P Dimova, T Djémié, P Gormley, R Guerrini, I Helbig, H Hjalgrim, D Hoffman-Zacharska, J Jähn, KM Klein, B Koeleman, V Komarek, R Krause

2014-01-01

Emerging evidence indicates that epileptic encephalopathies are genetically highly heterogeneous, underscoring the need for large ..

KCNT1 gain of function in 2 epilepsy phenotypes is reversed by quinidine

CJ Milligan, M Li, EV Gazina, SE Heron, U Nair, C Trager, CA Reid, A Venkat, DP Younkin, DJ Dlugos, S Petrovski, DB Goldstein, LM Dibbens, IE Scheffer, SF Berkovic, S Petrou

2014-01-01

Objective Mutations in KCNT1 have been implicated in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and epilepsy of i..

De novo mutations in epileptic encephalopathies

AS Allen, SF Berkovic, P Cossette, N Delanty, D Dlugos, EE Eichler, MP Epstein, T Glauser, DB Goldstein, Y Han, EL Heinzen, Y Hitomi, KB Howell, MR Johnson, R Kuzniecky, DH Lowenstein, YF Lu, MRZ Madou, AG Marson, HC Mefford

2013-08-13

Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. He..

Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes

S Petrovski, Q Wang, EL Heinzen, AS Allen, DB Goldstein

2013-08-01

A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progre..

Epi4K: Gene discovery in 4,000 genomes

Sam Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan Eichler, Michael Epstein, Tracy Glauser, David Goldstein, Erin Heinzen, Michael R Johnson, Ruben Kuzniecky, Daniel Lowenstein, Tony Marson, Heather Mefford, Terence O'Brien, Ruth Ottman, Ann Poduri, Ingrid Scheffer, Elliott Sherr, Kevin Shianna

2012-08-01

A major challenge in epilepsy research is to unravel the complex genetic mechanisms underlying both common and rare forms of epile..