3 of 7 Epi4K: Gene discovery in 4,000 epilepsy genomes

Diverse genetic causes of polymicrogyria with epilepsy

Andrew S Allen, Vimla Aggarwal, Samuel F Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan E Eichler, Michael P Epstein, Catharine Freyer, David B Goldstein, Renzo Guerrini, Tracy Glauser, Erin L Heinzen, Michael R Johnson, Ruben Kuzniecky, Daniel H Lowenstein, Anthony G Marson, Heather C Mefford, Terence J O'Brien, Ruth Ottman

2021-04-05

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

Sahar Gelfman, Sarah Dugger, Cristiane de Araujo Martins Moreno, Zhong Ren, Charles J Wolock, Neil A Shneider, Hemali Phatnani, Elizabeth T Cirulli, Brittany N Lasseigne, Tim Harris, Tom Maniatis, Guy A Rouleau, Robert H Brown, Aaron D Gitler, Richard M Myers, Slave Petrovski, Andrew Allen, David B Goldstein, Matthew B 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

Samuel F Berkovic, David B Goldstein, Erin L Heinzen, Brandon L Laughlin, Daniel H Lowenstein, Laura Lubbers, Randall Stewart, Vicky Whittemore, Kaitlin Angione, Carl W Bazil, Louise Bier, Judith Bluvstein, Elise Brimble, Colleen Campbell, Gianpiero Cavalleri, Chelsea Chambers, Hyunmi Choi, Maria Roberta Cilio, Michael Ciliberto, Susannah Cornes

2019-05-01

OBJECTIVE: The Epilepsy Genetics Initiative (EGI) was formed in 2014 to create a centrally managed database of clinically generate..

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

Benjamin Cogne, Sophie Ehresmann, Eliane Beauregard-Lacroix, Justine Rousseau, Thomas Besnard, Thomas Garcia, Slave Petrovski, Shiri Avni, Kirsty McWalter, Patrick R Blackburn, Stephan J Sanders, Kevin Uguen, Jacqueline Harris, Julie S Cohen, Moira Blyth, Anna Lehman, Jonathan Berg, Mindy H Li, Usha Kini, Shelagh 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

Neha S Raghavan, Adam M Brickman, Howard Andrews, Jennifer J Manly, Nicole Schupf, Rafael Lantigua, Charles J Wolock, Sitharthan Kamalakaran, Slave Petrovski, Giuseppe Tosto, Badri N Vardarajan, David B Goldstein, Richard 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

Erin L Heinzen, Adam C O'Neill, Xiaolin Zhu, Andrew S Allen, Melanie Bahlo, Jamel Chelly, Ming Hui Chen, William B Dobyns, Saskia Freytag, Renzo Guerrini, Richard J Leventer, Annapurna Poduri, Stephen P Robertson, Christopher A Walsh, Mengqi 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

Samuel F Berkovic, Tracy Dixon-Salazar, David B Goldstein, Erin L Heinzen, Brandon L Laughlin, Daniel H Lowenstein, Laura Lubbers, Julie Milder, Randall Stewart, Vicky Whittemore, Kaitlin Angione, Carl W Bazil, Louise Bier, Judith Bluvstein, Elise Brimble, Colleen Campbell, Chelsea Chambers, Hyunmi Choi, Maria Roberta Cilio, Michael Ciliberto

2018-02-01

PurposeAs part of the Epilepsy Genetics Initiative, we re-evaluated clinically generated exome sequence data from 54 epilepsy pati..

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

Xiaolin Zhu, Raghavendra Padmanabhan, Brett Copeland, Joshua Bridgers, Zhong Ren, Sitharthan Kamalakaran, Ailbhe O'Driscoll-Collins, Samuel F Berkovic, Ingrid E Scheffer, Annapurna Poduri, Davide Mei, Renzo Guerrini, Daniel H Lowenstein, Andrew S Allen, Erin L Heinzen, David B 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

Candace T Myers, Nicholas Stong, Emily I Mountier, Katherine L Helbig, Saskia Freytag, Joseph E Sullivan, Bruria Ben Zeev, Andreea Nissenkorn, Michal Tzadok, Gali Heimer, Deepali N Shinde, Arezoo Rezazadeh, Brigid M Regan, Karen L Oliver, Michelle E Ernst, Natalie C Lippa, Maureen S Mulhern, Zhong Ren, Annapurna Poduri, Danielle M 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 non-coding genome that are intolerant to variation using population genetics

Ayal B Gussow, Brett R Copeland, Ryan S Dhindsa, Quanli Wang, Slave A Petrovski, William H Majoros, Andrew S Allen, David B Goldstein

2017-08-10

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

Annotating pathogenic non-coding variants in genic regions

Sahar Gelfman, Quanli Wang, K Melodi McSweeney, Zhong Ren, Francesca La Carpia, Matt Halvorsen, Kelly Schoch, Fanni Ratzon, Erin L Heinzen, Michael J Boland, Slave Petrovski, David B Goldstein

2017-08-09

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

Phenotypic analysis of 303 multiplex families with common epilepsies

Bassel Abou-Khalil, Zaid Afawi, Andrew S Allen, Jocelyn F Bautista, Susannah T Bellows, Samuel F Berkovic, Judith Bluvstein, Rosemary Burgess, Gregory Cascino, Elisa J Cops, Patrick Cossette, Sabrina Cristofaro, Douglas E Crompton, Norman Delanty, Orrin Devinsky, Dennis Dlugos, Michael P Epstein, Nathan B Fountain, Catharine Freyer, Sarah I 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 A new disease of vesicle fission

Sarah von Spiczak, Katherine L Helbig, Deepali N Shinde, Robert Huether, Manuela Pendziwiat, Charles Lourenco, Mark E Nunes, Dean P Sarco, Richard A Kaplan, Dennis J Dlugos, Heidi Kirsch, Anne Slavotinek, Maria R Cilio, Mackenzie C Cervenka, Julie S Cohen, Rebecca McClellan, Ali Fatemi, Amy Yuen, Yoshimi Sagawa, Rebecca 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

Andrew S Allen, Samuel F Berkovic, Joshua Bridgers, Patrick Cossette, Dennis Dlugos, Michael P Epstein, Tracy Glauser, David B Goldstein, Erin L Heinzen, Yu Jiang, Michael R Johnson, Ruben Kuzniecky, Daniel H Lowenstein, Anthony G Marson, Heather C Mefford, Terence J O'Brien, Ruth Ottman, Steven Petrou, Slave Petrovski, Annapurna Poduri

2017-06-01

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

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

Candace T Myers, Jacinta M McMahon, Amy L Schneider, Slave Petrovski, Andrew S Allen, Gemma L Carvill, Matthew Zemel, Julia E Say-Kally, Amy J LaCroix, Erin L Heinzen, Georgina Hollingsworth, Marina Nikanorova, Mark Corbett, Jozef Gecz, David Coman, Jeremy Freeman, Sophie Calvert, Deepak Gill, Patrick Carney, Tally 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.

Slavé Petrovski, Roberta E Parrott, Joseph L Roberts, Hongxiang Huang, Jialong Yang, Balachandra Gorentla, Talal Mousallem, Endi Wang, Martin Armstrong, Duncan McHale, Nancie J MacIver, David B Goldstein, Xiao-Ping Zhong, Rebecca H 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

Matt Halvorsen, Slave Petrovski, Renee Shellhaas, Yingying Tang, Laura Crandall, David Goldstein, Orrin Devinsky

2016-07-01

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

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

Ayal B Gussow, Slave Petrovski, Quanli Wang, Andrew S Allen, David B 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

F 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

Xiaolin Zhu, Slave Petrovski, Pingxing Xie, Elizabeth K Ruzzo, Yi-Fan Lu, K Melodi McSweeney, Bruria Ben-Zeev, Andreea Nissenkorn, Yair Anikster, Danit Oz-Levi, Ryan S Dhindsa, Yuki Hitomi, Kelly Schoch, Rebecca C Spillmann, Gali Heimer, Dina Marek-Yagel, Michal Tzadok, Yujun Han, Gordon Worley, Jennifer Goldstein

2015-10-01

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

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

Slave Petrovski, Ayal B Gussow, Quanli Wang, Matt Halvorsen, Yujun Han, William H Weir, Andrew S Allen, David B Goldstein

2015-09-01

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

Incorporating Functional Information in Tests of Excess De Novo Mutational Load

Yu Jiang, Yujun Han, Slave Petrovski, Kouros Owzar, David B Goldstein, Andrew S 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

Ryan S Dhindsa, Shelton S Bradrick, Xiaodi Yao, Erin L Heinzen, Slave Petrovski, Brian J Krueger, Michael R Johnson, Wayne N Frankel, Steven Petrou, Rebecca M Boumil, David B Goldstein

2015-06-01

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

De Novo Mutations in Synaptic Transmission Genes Including DNM1 Cause Epileptic Encephalopathies

Silke Appenzeller, Rudi Balling, Nina Barisic, Stephanie Baulac, Hande Caglayan, Dana Craiu, Peter De Jonghe, Christel Depienne, Petia Dimova, Tania Djemie, Padhraig Gormley, Renzo Guerrini, Ingo Helbig, Helle Hjalgrim, Dorota Hoffman-Zacharska, Johanna Jaehn, Karl Martin Klein, Bobby Koeleman, Vladimir Komarek, Roland Krause

2014-10-02

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

Carol J Milligan, Melody Li, Elena V Gazina, Sarah E Heron, Umesh Nair, Chantel Trager, Christopher A Reid, Anu Venkat, Donald P Younkin, Dennis J Dlugos, Slave Petrovski, David B Goldstein, Leanne M Dibbens, Ingrid E Scheffer, Samuel F Berkovic, Steven Petrou

2014-04-01

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

De novo mutations in epileptic encephalopathies

Andrew S Allen, Samuel F Berkovic, Patrick Cossette, Norman Delanty, Dennis Dlugos, Evan E Eichler, Michael P Epstein, Tracy Glauser, David B Goldstein, Yujun Han, Erin L Heinzen, Yuki Hitomi, Katherine B Howell, Michael R Johnson, Ruben Kuzniecky, Daniel H Lowenstein, Yi-Fan Lu, Maura RZ Madou, Anthony G Marson, Heather C Mefford

2013-09-12

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

Slave Petrovski, Quanli Wang, Erin L Heinzen, Andrew S Allen, David B 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..