Evidence map›Paper›PMID 30827496›Full record

ArticleAmerican journal of human genetics2019

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

Benjamin Cogné, Sophie Ehresmann, Eliane Beauregard-Lacroix, Justine Rousseau, Thomas Besnard, Thomas Garcia, Slavé Petrovski, Shiri Avni, Kirsty McWalter, Patrick R Blackburn and 107 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
5.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 52 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

117 authors at 20 institutions in 8 countries.

Benjamin CognéCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Sophie EhresmannCentre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada.
Eliane Beauregard-LacroixCentre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada.
Justine RousseauCentre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada.
Thomas BesnardCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Thomas GarciaCentre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada.
Slavé PetrovskiDepartment of Medicine, University of Melbourne, Austin Health and Royal Melbourne Hospital, Melbourne, VIC 3010, Australia; AstraZeneca Centre for Genomics Research, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca, Cambridge CB2 0AA, UK.
Shiri AvniVisual Geometry Group, Department of Engineering Science, University of Oxford, Oxford OX1 3PJ, UK.
Kirsty McWalterGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Patrick R BlackburnDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Center for Individualized Medicine, Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Stephan J SandersDepartment of Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Kévin UguenUMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Inserm, L'Etablissement Français du Sang, Institut Brestois Santé Agro Matière, Université de Brest Occidentale, 29200 Brest, France; Service de Génétique médicale et de biologie de la reproduction, Centre Hospitalier Regional Universitaire Brest, 29200 Brest, France.
Jacqueline HarrisDivision of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Julie S CohenDivision of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD 21205, USA; Hugo W. Moser Research Institute, Kennedy Krieger Institute, Baltimore, MD 21205, USA.
Moira BlythDepartment of Clinical Genetics, Chapel Allerton Hospital, Yorkshire Regional Genetics Service, Leeds Teaching Hospitals National Health Service Trust, Chapeltown Road, Leeds LS7 4SA, UK.
Anna LehmanDepartment of Pediatrics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Jonathan BergMolecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Mindy H LiRush University Medical Center, Department of Pediatrics, Division of Genetics, Chicago, IL 60612, USA.
Usha KiniOxford Centre for Genomic Medicine, Oxford University Hospitals National Health Service Trust, Oxford OX3 7LE, UK.
Shelagh JossWest of Scotland Regional Genetics Service, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK.
Charlotte von der LippeDepartment of Medical Genetics, St. Olav's Hospital, Trondheim University Hospital, 7006 Trondheim, Norway.
Christopher T GordonLaboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France.
Jennifer B HumbersonDivision of Genetics, Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, VA 22903, USA.
Laurie RobakDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA.
Daryl A ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX 77030, USA.
Vernon R SuttonDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
Cara M SkrabanDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Jennifer J JohnstonMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA.
Annapurna PoduriDivision of Epilepsy and Clinical Neurophysiology and Epilepsy Genetics Program, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Magnus NordenskjöldDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Vandana ShashiDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Erica H GerkesDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, 9700 RB, the Netherlands.
Ernie M H F BongersDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
Christian GilissenDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
Yuri A ZarateSection of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
Malin KvarnungDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Kevin P LallyDepartment of Pediatric Surgery, The McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital, Houston, TX 77030, USA.
Peggy A KulchDivision of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ 85016, USA.
Brina DanielsSection of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.
Andres Hernandez-GarciaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Nicholas StongInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
Julie McGaughranGenetic Health Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland 4029, Australia; School of Medicine, The University of Queensland, Brisbane, Queensland 4029, Australia.
Kyle RettererGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Kristian TvetenDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Jennifer SullivanDivision of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Madeleine R GeishekerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
Asbjorg Stray-PedersenNorwegian National Unit for Newborn Screening, Division of Pediatric and Adolecent Medicine, Oslo University Hospital, Rikshospitalet, Pb 4950 Nydalen, N-0424 Oslo, Norway.
Jennifer M TarpinianRoberts Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Eric W KleeDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA; Center for Individualized Medicine, Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Julie C SappMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA.
Jacob ZyskindGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Øystein L HollaDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Emma BedoukianRoberts Individualized Medical Genetics Center, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Francesca FilippiniLaboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France.
Anne GuimierLaboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France; Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), 75015 Paris, France.
Arnaud PicardParis Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France; Service de Chirurgie Maxillofaciale et Plastique, Centre de référence des Malformations de la Face et de la Cavité Buccale, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), 75015 Paris, France.
Øyvind L BuskDepartment of Medical Genetics, Telemark Hospital Trust, 3710 Skien, Norway.
Jaya PunethaDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Rolph PfundtDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
Anna LindstrandDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Ann NordgrenDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, 17176 Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, 17176 Stockholm, Sweden.
Fayth KalbDivision of Genetics, Birth Defects, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Megha DesaiGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Ashley Harmon EbanksDepartment of Pediatric Surgery, The McGovern Medical School at the University of Texas Health Science Center and Children's Memorial Hermann Hospital, Houston, TX 77030, USA.
Shalini N JhangianiHuman Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA.
Tammie DewanDepartment of Pediatrics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Zeynep H Coban AkdemirDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Aida TelegrafiGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Elaine H ZackaiDivision of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Amber BegtrupGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Xiaofei SongDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Annick ToutainService de Génétique, Centre Hospitalier Universitaire de Tours, 2 Boulevard Tonnellé, 37044 Tours, France; Inserm U1253, Ibrain, Université de Tours, 37032 Tours, France.
Ingrid M WentzensenGeneDx, 207 Perry Parkway, Gaithersburg, MD 20877, USA.
Sylvie OdentService de Génétique Clinique, Centre Référence Déficiences Intellectuelles de Causes Rares, Centre de Référence Anomalies du Développement, Centre Labellisé pour les Anomalies du Développement (CLAD) Ouest, Centre Hospitalier Universitaire de Rennes, 35203 Rennes, France; Institut de Génétique et Développement de Rennes, UMR 6290, Université de Rennes, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France.
Dominique BonneauCentre Hospitalier Universitaire de Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France; Mitochondrial and Cardiovascular Pathophysiology (MITOVASC), Unité mixte de Recherche, Centre National de la Recherche Scientifique 6015, Inserm 1083, Université d'Angers, 49933 Angers, France.
Xénia LatypovaCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Wallid DebCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
CAUSES StudyDepartment of Pediatrics, University of British Columbia, Vancouver, BC V6H 3N1, Canada.
Sylvia RedonUMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Inserm, L'Etablissement Français du Sang, Institut Brestois Santé Agro Matière, Université de Brest Occidentale, 29200 Brest, France; Service de Génétique médicale et de biologie de la reproduction, Centre Hospitalier Regional Universitaire Brest, 29200 Brest, France.
Frédéric BilanCentre Hospitalier Universitaire de Poitiers, Service de Génétique, BP577, 86021 Poitiers, France; Equipe d'accueil 3808, Université Poitiers, Poitiers 86034, France.
Marine LegendreCentre Hospitalier Universitaire de Poitiers, Service de Génétique, BP577, 86021 Poitiers, France; Equipe d'accueil 3808, Université Poitiers, Poitiers 86034, France.
Caitlin TroyerDivision of Genetics, Department of Pediatrics, University of Virginia Children's Hospital, Charlottesville, VA 22903, USA.
Kerri WhitlockDepartment of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Oana CaluseriuDepartment of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada.
Marine I MurphreeDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Pavel N PichurinDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Katherine AgreDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Ralitza GavrilovaDepartment of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA; Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Tuula RinneDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, 6525 GA, the Netherlands.
Meredith ParkEpilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA.
Catherine ShainDepartment of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Erin L HeinzenInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
Rui XiaoDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
Jeanne AmielLaboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France; Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), 75015 Paris, France.
Stanislas LyonnetLaboratory of Embryology and Genetics of Human Malformations, Institut National de la Santé et de la Recherche Médicale (Inserm), UMR 1163, Institut Imagine, 75015 Paris, France; Paris Descartes-Sorbonne Paris Cité University, Institut Imagine, 75015 Paris, France; Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris (APHP), 75015 Paris, France.
Bertrand IsidorCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Leslie G BieseckerMedical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-4472, USA.
Dan LowensteinDepartment of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
Jennifer E PoseyDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Anne-Sophie Denommé-PichonCentre Hospitalier Universitaire de Angers, Département de Biochimie et Génétique, 49933 Angers Cedex 9, France; Mitochondrial and Cardiovascular Pathophysiology (MITOVASC), Unité mixte de Recherche, Centre National de la Recherche Scientifique 6015, Inserm 1083, Université d'Angers, 49933 Angers, France.
Deciphering Developmental Disorders studyWellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
Claude FérecUMR 1078, Génétique, Génomique Fonctionnelle et Biotechnologies, Inserm, L'Etablissement Français du Sang, Institut Brestois Santé Agro Matière, Université de Brest Occidentale, 29200 Brest, France; Service de Génétique médicale et de biologie de la reproduction, Centre Hospitalier Regional Universitaire Brest, 29200 Brest, France.
Xiang-Jiao YangRosalind & Morris Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, QC H3A 1A3, Canada; Department of Biochemistry, McGill University and McGill University Health Center, Montreal, QC H3A 1A3, Canada.
Jill A RosenfeldDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Brigitte Gilbert-DussardierCentre Hospitalier Universitaire de Poitiers, Service de Génétique, BP577, 86021 Poitiers, France; Equipe d'accueil 3808, Université Poitiers, Poitiers 86034, France.
Séverine Audebert-BellangerService de Génétique médicale et de biologie de la reproduction, Centre Hospitalier Regional Universitaire Brest, 29200 Brest, France.
Richard RedonINSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Holly A F StessmanDepartment of Pharmacology, Creighton University Medical School, Omaha, NE 68178, USA.
Christoffer NellakerNuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7FZ, UK.
Yaping YangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Baylor Genetics, Houston, TX 77021, USA.
James R LupskiDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
David B GoldsteinInstitute for Genomic Medicine, Columbia University, New York, NY 10032, USA.
Evan E EichlerDepartment of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Francois BolducDepartment of Medical Genetics, University of Alberta, Edmonton, AB T6G 2H7, Canada; Division of Pediatric Neurology, University of Alberta, Edmonton, AB, Canada; Neuroscience and Mental Health Institute, University of Alberta, Edmonton, AB, Canada.
Stéphane BézieauCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France.
Sébastien KüryCentre Hospitalier Universitaire de Nantes, Service de Génétique Médicale, 9 quai Moncousu, 44093 Nantes, France; INSERM, CNRS, UNIV Nantes, l'institut du thorax, 44007 Nantes, France. Electronic address: sebastien.kury@chu-nantes.fr.
Philippe M CampeauCentre Hospitalier Universitaire Sainte-Justine Research Centre, University of Montreal, Montreal, QC H3T 1C5, Canada; Department of Pediatrics, University of Montreal, Montreal, QC H3T1J4, Canada. Electronic address: p.campeau@umontreal.ca.
Baylor College of Medicine · USInserm · FRCentre Hospitalier Universitaire Sainte-Justine · CAMayo Clinic in Florida · USChildren's Hospital of Philadelphia · USColumbia University · USKarolinska Institutet · SENational Human Genome Research Institute · USRadboud University Medical Center · NLTelemark Hospital · NOUniversity of Oxford · GBBaylor Genetics · USCentre Hospitalier Régional Universitaire de Brest · FRCentre Hospitalier Universitaire de Poitiers · FRCentre National de la Recherche Scientifique · FRDuke Medical Center · USHarvard University · USHôpital Necker-Enfants Malades · FRInstitut du Thorax · FRKennedy Krieger Institute · US

Funding

University of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4M
Rare & Mosaic Disorders Molecular ResearchZIAHG200328 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE · 2009 to 2025
$26.8M
The Epilepsy Phenome/ Genome Project (EPGP)U01NS053998 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2007 to 2013
$26.4M
Baylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5M
3 of 7 Epi4K: Sequencing, Biostatistics & Bioinformatics CoreU01NS077303 · NINDS · DUKE UNIVERSITY · PI EICHLER, EVAN, GOLDSTEIN, DAVID B. · 2011 to 2018
$13.3M
Sporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2M
Intellectual and Developmental Disabilities Research CenterU54HD083091 · NICHD · UNIVERSITY OF WASHINGTON · PI GARDEN, GWENN A · 2014 to 2019
$7.9M
The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI SCHULTZ, ROBERT THOMAS · 2016 to 2020
$6.3M
STRUCTURAL VARIATION IN NEUROLOGICAL DISEASER35NS105078 · NINDS · BAYLOR COLLEGE OF MEDICINE · PI LUPSKI, JAMES R. · 2018 to 2025
$6.0M
Clinical and Molecular Studies of MalformationsZ01HG200328 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BIESECKER, LESLIE G · 2005 to 2008
$5.5M
2 of 7 EPI4K - Phenotyping Clinical Informatics Core U01NS077276 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOWENSTEIN, DANIEL H · 2011 to 2015
$3.1M
Retinoid-Related Genes in Diaphragm and Cardiac DevelopmentR01HD064667 · NICHD · BAYLOR COLLEGE OF MEDICINE · PI SCOTT, DARYL ARMSTRONG · 2010 to 2014
$1.5M
CIHRIntramural NIH HHS Z01 HG200328Medical Research Council MR/M014568/1NHGRI NIH HHS K08 HG008986NHGRI NIH HHS UM1 HG006542NICHD NIH HHS R01 HD064667NICHD NIH HHS U54 HD083091NICHD NIH HHS U54 HD086984NIGMS NIH HHS T32 GM007266NIMH NIH HHS R01 MH101221NINDS NIH HHS R35 NS105078NINDS NIH HHS U01 NS053998NINDS NIH HHS U01 NS077274NINDS NIH HHS U01 NS077276NINDS NIH HHS U01 NS077303NINDS NIH HHS U01 NS077364
6 · The paper itself

Abstract

Acetylation of the lysine residues in histones and other DNA-binding proteins plays a major role in regulation of eukaryotic gene expression. This process is controlled by histone acetyltransferases (HATs/KATs) found in multiprotein complexes that are recruited to chromatin by the scaffolding subunit transformation/transcription domain-associated protein (TRRAP). TRRAP is evolutionarily conserved and is among the top five genes intolerant to missense variation. Through an international collaboration, 17 distinct de novo or apparently de novo variants were identified in TRRAP in 24 individuals. A strong genotype-phenotype correlation was observed with two distinct clinical spectra. The first is a complex, multi-systemic syndrome associated with various malformations of the brain, heart, kidneys, and genitourinary system and characterized by a wide range of intellectual functioning; a number of affected individuals have intellectual disability (ID) and markedly impaired basic life functions. Individuals with this phenotype had missense variants clustering around the c.3127G>A p.(Ala1043Thr) variant identified in five individuals. The second spectrum manifested with autism spectrum disorder (ASD) and/or ID and epilepsy. Facial dysmorphism was seen in both groups and included upslanted palpebral fissures, epicanthus, telecanthus, a wide nasal bridge and ridge, a broad and smooth philtrum, and a thin upper lip. RNA sequencing analysis of skin fibroblasts derived from affected individuals skin fibroblasts showed significant changes in the expression of several genes implicated in neuronal function and ion transport. Thus, we describe here the clinical spectrum associated with TRRAP pathogenic missense variants, and we suggest a genotype-phenotype correlation useful for clinical evaluation of the pathogenicity of the variants.

Indexed as

Mutation, MissenseAdaptor Proteins, Signal TransducingAdolescentAdultAmino Acid SequenceAutistic DisorderChildChild, PreschoolFemaleGenetic Association StudiesHumansInfantIntellectual DisabilityMaleNuclear ProteinsPrognosisAdaptor Proteins, Signal TransducingNuclear Proteinstransformation-transcription domain-associated proteinautism spectrum disordercongenital malformationsde novo variantshistone acetylationintellectual disabilityneurodevelopmental disordersTRRAP

Identifiers

PMID30827496
PMCPMC6407527
OpenAlexW2918517022

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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.