SynthesisAmerican journal of human genetics2017
High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in American journal of human genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 235 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
235citing papers in PubMed, 3 pooled it
36.1field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
235 citing papers in PubMed, 3 syntheses or guidelines pooled it, 451 citations in OpenAlex.
- Prenatal Characterization of Houge-Janssens Syndrome Type 2: A Case Report and Systematic Review of Fetal Phenotypes Associated With PPP2R1A Mutations.Molecular genetics & genomic medicine · 2025Pooled it
- Cys-loop receptors on cannabinoids: All high?Frontiers in physiology · 2022Pooled it
- Genetic Neonatal-Onset Epilepsies and Developmental/Epileptic Encephalopathies with Movement Disorders: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Genomic analyses implicate noncoding de novo variants in congenital heart disease.Nature genetics · 2020Trial
- Novel SZT2 mutations in three patients with developmental and epileptic encephalopathies.Molecular genetics & genomic medicine · 2019Trial
- Article
- Clinical and Genetic Analysis of Pediatric Neurodevelopmental Disorders With Complex Chromosomal Rearrangements in Two Cases.Molecular genetics & genomic medicine · 2026Article
- Lithium as a therapeutic strategy for SNAP25 encephalopathies via modulation of homeostatic plasticity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The genetic architecture of epilepsy across molecular mechanisms and clinical heterogeneity.Epilepsia open · 2026Review
- Article
- Pathogenic mutations in clathrin heavy chain disrupt synapse architecture and learning iniScience · 2026Article
- Autosomal allelic inactivation at loci with variable replication timing and dosage sensitivity.eLife · 2026Article
- Phenotypic diversity is caused by non-linear genetic interactions between two SNAREopathy genes.Molecular psychiatry · 2026Article
- Functional evidence for SCN8A splice-donor variant c.4419+1 A > G causing loss of function.Human genome variation · 2026Article
- Normalization of network activity in an epilepsy model with a constitutively active GABBR2 variant.Brain : a journal of neurology · 2026Article
- Carrier screening in the reproductive setting-Are there medical implications for the heterozygote?-A guide for clinicians.Pregnancy (Hoboken, N.J.) · 2026Review
- Predictive value of seizure onset for gross motor dysfunction in individuals with pathogenic GABRB2 and GABRB3 variants.Epilepsia · 2026Article
- Encephalopathy-linked UFM1 variants impede neuronal protein translation, development, and function.EMBO molecular medicine · 2026Article
- Evolutionary divergence and functional insights into the heteromeric cis-prenyltransferase of Paramecium tetraurelia.The FEBS journal · 2026Article
- Human neuronal networks on micro-electrode arrays as a tool to assess genotype-phenotype correlation in CACNA1A-related disorders.Stem cell reports · 2026Article
175 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
107 authors at 20 institutions in 10 countries.
Fadi F HamdanCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada.
Candace T MyersDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA 98195, USA.
Patrick CossetteCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada.
Philippe LemayCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada.
Dan SpiegelmanMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada.
Alexandre Dionne LaporteMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada.
Christina NassifCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada.
Ousmane DialloMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada.
Jean MonlongMcGill University and Genome Quebec Innovation Center, Montreal, QC H3A 1A4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Maxime Cadieux-DionCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA; Department of Pathology and Laboratory Medicine, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
Sylvia DobrzenieckaCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada.
Caroline MelocheCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada.
Kyle RettererGeneDx, Gaithersburg, MD 20877, USA.
Megan T ChoGeneDx, Gaithersburg, MD 20877, USA.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Weimin BiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Miraca Genetics Laboratories, Baylor College of Medicine, Houston, TX 77021, USA.
Christine MassicotteCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada.
Marguerite MiguetCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada.
Ledia BrungaProgram in Genetics and Genome Biology, Division of Neurology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON M5G 0A4, Canada.
Brigid M ReganDivision of Neurology, Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada.
Kelly MoDivision of Neurology, Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada.
Cory TamDivision of Neurology, Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada.
Amy SchneiderEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.
Georgie HollingsworthEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.
Deciphering Developmental Disorders StudyWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
David R FitzPatrickMRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK.
Alan DonaldsonClinical Genetics Service, University Hospitals Bristol NHS Foundation Trust, St. Michael's Hospital, St. Michael's Hill, Bristol BS2 8DT, UK.
Natalie CanhamNorth West Thames Regional Genetics Service, London North West Healthcare NHS Trust, Northwick Park Hospital, Watford Road, Harrow HA1 3UJ, UK.
Edward BlairOxford Centre for Genomic Medicine, ACE building Nuffield Orthopaedic Centre, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 7HE, UK.
Bronwyn KerrManchester Centre for Genomic Medicine, St. Mary's Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK.
Andrew E FryInstitute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK.
Rhys H ThomasMRC Centre for Neuropsychiatric Genetics & Genomics, Hadyn Ellis Building, Cathays, Cardiff University, Cardiff CF24 4HQ, UK.
Joss ShelaghWest of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
Jane A HurstNorth East Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London WC1N 3JH, UK.
Helen BrittainNorth East Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London WC1N 3JH, UK.
Moira BlythYorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK.
Robert Roger LebelDepartment of Pediatrics, Section of Medical Genetics, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Erica H GerkesUniversity of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, the Netherlands.
Laura Davis-KeppenUniversity of South Dakota Sanford School of Medicine, Sioux Falls, SD 57117, USA.
Quinn SteinAugustana-Sanford Genetic Counseling Graduate Program, Sioux Falls, SD 57197, USA.
Wendy K ChungDepartments of Medicine and Pediatrics, Columbia University Medical Center, New York, NY 10032, USA.
Sara J DorisonBaptist Hospital, Miami, FL 33176 USA.
Paul J BenkeJoe DiMaggio Children's Hospital, Hollywood, FL 33021, USA.
Emily FassiDivision of Genetics and Genomic Medicine, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Nicole Corsten-JanssenUniversity of Groningen, University Medical Center Groningen, Department of Genetics, 9700 RB Groningen, the Netherlands.
Erik-Jan KamsteegDepartment of Human Genetics, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, 6500 HB Nijmegen, the Netherlands.
Frederic T Mau-ThemCentre de Génétique des Anomalies du Développement, Centre Hospitalier Universitaire de Dijon, 21000 Dijon, France; Équipe INSERM 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21000 Dijon, France.
Ange-Line BruelCentre de Génétique des Anomalies du Développement, Centre Hospitalier Universitaire de Dijon, 21000 Dijon, France; Équipe INSERM 1231, Génétique des Anomalies du Développement, Université de Bourgogne, 21000 Dijon, France.
Alain VerloesGenetics Department, Assistance Publique - Hôpitaux de Paris, Robert-Debré University Hospital, 75000 Paris, France.
Katrin ÕunapDepartment of Clinical Genetics, United Laboratories, Tartu University Hospital and Institute of Clinical Medicine, University of Tartu, Tartu 51014, Estonia.
Monica H WojcikDivision of Genetics and Genomics and Division of Newborn Medicine, Department of Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Dara V F AlbertNationwide Children's Hospital and Ohio State University, Department of Pediatrics, Division of Neurology, Columbus, OH 43205, USA.
Sunita VenkateswaranDivision of Neurology, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada.
Tyson WareUniversity of Tasmania, Royal Hobart Hospital, Department of Paediatrics, Hobart, TAS 7000, Australia.
Dean JonesSchool of Medicine, University of Tasmania, Hobart, TAS 7000, Australia.
Yu-Chi LiuPopulation Health and Immunity Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.
Shekeeb S MohammadChildren's Hospital at Westmead Clinical School, University of Sydney, Westmead, NSW 2145, Australia.
Peyman BizargityDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Carlos A BacinoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Vincenzo LeuzziDipartimento di Pediatria e di Neuropsichiatria Infantile, Università La Sapienza, 00185 Rome, Italy.
Simone MartinelliDipartimento di Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, 00161 Rome, Italy.
Bruno DallapiccolaGenetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy.
Marco TartagliaGenetics and Rare Diseases Research Division, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico, 00165 Rome, Italy.
Lubov BlumkinMetabolic Neurogenetic Clinic and Pediatric Movement Disorders Clinic, Wolfson Medical Center, Holon 5822012, Israel.
Klaas J WierengaUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Gabriela PurcarinUniversity of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
James J O'ByrneUniversity of British Columbia, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada.
Sylvia StocklerUniversity of British Columbia, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada.
Anna LehmanDepartment of Medical Genetics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Boris KerenDépartement de Génétique, Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique "Déficiences Intellectuelles et Autisme," Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, Paris 75013, France; Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), UMRS 1127, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris 75013, France.
Marie-Christine NouguesAssistance Publique - Hôpitaux de Paris, Hôpital d'Enfants Armand Trousseau, Service de Neuropédiatrie, Paris 75012, France.
Cyril MignotDépartement de Génétique, Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique "Déficiences Intellectuelles et Autisme," Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, Paris 75013, France; Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), UMRS 1127, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris 75013, France.
Stéphane AuvinUniversité Paris Diderot, Sorbonne Paris Cité, INSERM UMR 1141, Paris 75019, France; Assistance Publique - Hôpitaux de Paris, Hôpital Robert Debré, Service de Neurologie Pédiatrique, Paris 75019, France.
Caroline NavaDépartement de Génétique, Centre de Référence des Déficiences Intellectuelles de Causes Rares, Groupe de Recherche Clinique "Déficiences Intellectuelles et Autisme," Université Pierre et Marie Curie, Hôpital de la Pitié-Salpêtrière, Paris 75013, France; Sorbonne Universités, Université Pierre et Marie Curie (Université Paris 06), UMRS 1127, INSERM U 1127, CNRS UMR 7225, Institut du Cerveau et de la Moelle Épinière, Paris 75013, France.
Susan M HiattHudsonAlpha Institute for Biotechnology, 601 Genome Way, Huntsville, AL 35806, USA.
Martina BebinDepartment of Neurology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Yunru ShaoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Fernando ScagliaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Seema R LalaniDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Richard E FryeDepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA; Arkansas Children's Research Institute, Little Rock, AR 72205, USA.
Imad T JarjourTexas Children's Hospital and Baylor College of Medicine, Houston, TX 77030, USA.
Stéphanie JacquesCentre Hospitalier Rouyn-Noranda, Rouyn-Noranda, QC J9X 2B2, Canada.
Renee-Myriam BoucherDivision of Neurology, Centre Hospitalier Universitaire de Québec, Quebec, QC G1V 4G2, Canada.
Emilie RiouDepartment of Pediatrics, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
Myriam SrourDepartment of Pediatrics, McGill University, Montreal, QC H3A 1A4, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A 1A4, Canada.
Lionel CarmantCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Anne LortieDepartment of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Philippe MajorDepartment of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Paola DiadoriDepartment of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
François DubeauMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada.
Guy D'AnjouDepartment of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Guillaume BourqueMcGill University and Genome Quebec Innovation Center, Montreal, QC H3A 1A4, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada.
Samuel F BerkovicEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia.
Lynette G SadleirDepartment of Pediatrics and Child Health, University of Otago, Wellington 9016, New Zealand.
Philippe M CampeauCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Zoha KibarCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada.
Ronald G LafrenièreCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada.
Simon L GirardCentre Hospitalier de l'Université de Montréal Research Center, Montreal, QC H2X 0A9, Canada; Department of Human Genetics, McGill University, Montreal, QC H3A 1B1, Canada; Département des Sciences Fondamentales, Université du Québec à Chicoutimi, Chicoutimi, QC G7H 2B1, Canada.
Saadet Mercimek-MahmutogluDivision of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Cyrus BoelmanDivision of Neurology, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada.
Guy A RouleauMontreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, QC H3A2B4, Canada.
Ingrid E SchefferEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC 3084, Australia; Department of Pediatrics, University of Melbourne Royal Children's Hospital, Parkville, VIC 3052, Australia; Florey Institute of Neuroscience and Mental Health, Melbourne, VIC 3084, Australia.
Heather C MeffordDepartment of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, WA 98195, USA.
Danielle M AndradeDivision of Neurology, Epilepsy Genetics Program, Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, Toronto, ON M5G 2C4, Canada.
Elsa RossignolCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada.
Berge A MinassianProgram in Genetics and Genome Biology, Division of Neurology, Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON M5G 0A4, Canada; Division of Child Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX 75390, USA. Electronic address: berge.minassian@sickkids.ca.
Jacques L MichaudCentre Hospitalier Universitaire Sainte-Justine Research Center, Montreal, QC H3T1C5, Canada; Department of Neurosciences, Université de Montréal, Montreal, QC H3T1J4, Canada; Department of Pediatrics, Université de Montréal, Montreal, QC H3T1C5, Canada. Electronic address: jacques.michaud@recherche-ste-justine.qc.ca.
Centre Hospitalier Universitaire Sainte-Justine · CABaylor College of Medicine · USUniversity of Toronto · CAMontreal Neurological Institute and Hospital · CACentre Hospitalier de l’Université de Montréal · CAThe University of Melbourne · AUUniversité de Montréal · CACentre National de la Recherche Scientifique · FRInserm · FRUniversity of British Columbia · CABambino Gesù Children's Hospital · ITGreat Ormond Street Hospital · GBMcGill Genome Centre · CAUniversity Medical Center Groningen · NLUniversity of Oklahoma Health Sciences Center · USUniversity of Tasmania · AUUniversity of Washington · USArkansas Children's Hospital · USAssistance Publique – Hôpitaux de Paris · FRAugustana University · US
Funding
Joint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MTRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0MIntellectual and Developmental Disabilities Research CenterU54HD083091 · NICHD · UNIVERSITY OF WASHINGTON · PI DOHERTY, DANIEL · 2014 to 2019
$7.9MA Genomic Approach to EpilepsyR01NS069605 · NINDS · UNIVERSITY OF WASHINGTON · PI MEFFORD, HEATHER C. · 2010 to 2019
$4.9MA powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9MMedical Research Council MC_PC_U127561093NHGRI NIH HHS UM1 HG008900NICHD NIH HHS U54 HD083091NIGMS NIH HHS T32 GM007748NINDS NIH HHS R01 NS069605
Abstract
Developmental and epileptic encephalopathy (DEE) is a group of conditions characterized by the co-occurrence of epilepsy and intellectual disability (ID), typically with developmental plateauing or regression associated with frequent epileptiform activity. The cause of DEE remains unknown in the majority of cases. We performed whole-genome sequencing (WGS) in 197 individuals with unexplained DEE and pharmaco-resistant seizures and in their unaffected parents. We focused our attention on de novo mutations (DNMs) and identified candidate genes containing such variants. We sought to identify additional subjects with DNMs in these genes by performing targeted sequencing in another series of individuals with DEE and by mining various sequencing datasets. We also performed meta-analyses to document enrichment of DNMs in candidate genes by leveraging our WGS dataset with those of several DEE and ID series. By combining these strategies, we were able to provide a causal link between DEE and the following genes: NTRK2, GABRB2, CLTC, DHDDS, NUS1, RAB11A, GABBR2, and SNAP25. Overall, we established a molecular diagnosis in 63/197 (32%) individuals in our WGS series. The main cause of DEE in these individuals was de novo point mutations (53/63 solved cases), followed by inherited mutations (6/63 solved cases) and de novo CNVs (4/63 solved cases). De novo missense variants explained a larger proportion of individuals in our series than in other series that were primarily ascertained because of ID. Moreover, these DNMs were more frequently recurrent than those identified in ID series. These observations indicate that the genetic landscape of DEE might be different from that of ID without epilepsy.
Indexed as
Brain DiseasesChildChild, PreschoolEpilepsyFemaleGenome, HumanGenome-Wide Association StudyHumansIntellectual DisabilityMaleMutationRecurrenceSeizuresCLTCDHDDSepileptic encephalopathyGABBR2GABRB2NTRK2NUS1RAB11SNAP25
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.