文献

J-GLOBAL ID：202202279899853483   整理番号：22A1111905

複数のヒストンH4遺伝子を横切る再発性de novoミスセンス変異体は神経発達症候群の基礎となる【JST・京大機械翻訳】

Recurrent de novo missense variants across multiple histone H4 genes underlie a neurodevelopmental syndrome

著者 (74件)： Tessadori Federico (Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 Utrecht, the Netherlands) ,  Duran Karen (Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, the Netherlands) ,  Knapp Karen (Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand) ,  Fellner Matthias (Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand) ,  Smithson Sarah (Bristol Regional Genetics Service, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS2 8EG, UK) ,  Beleza Meireles Ana (Bristol Regional Genetics Service, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS2 8EG, UK) ,  Elting Mariet W. (Amsterdam UMC, Afdeling Klinische genetica, 1081 Amsterdam, the Netherlands) ,  Waisfisz Quinten (Amsterdam UMC, Afdeling Klinische genetica, 1081 Amsterdam, the Netherlands) ,  O’Donnell-Luria Anne (Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA) ,  O’Donnell-Luria Anne (Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA) ,  O’Donnell-Luria Anne (Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Nowak Catherine (Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Douglas Jessica (Manton Center for Orphan Disease Research, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Ronan Anne (Clinical Genetics, Hunter Genetics Unit, Waratah, NSW 2298, Australia) ,  Brunet Theresa (Institute of Medical Genetics, 81675 Munchen, Germany) ,  Brunet Theresa (Institute of Neurogenomics, Helmholtz Zentrum Muenchen, 85764 Neuherberg, Germany) ,  Kotzaeridou Urania (Division of Child Neurology and Inherited Metabolic Diseases, Department of Pediatrics, Heidelberg University Hospital, 69120 Heidelberg, Germany) ,  Svihovec Shayna (Section of Genetics and Metabolism, Department of Pediatrics, The Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA) ,  Saenz Margarita S. (Section of Genetics and Metabolism, Department of Pediatrics, The Children’s Hospital Colorado, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA) ,  Thiffault Isabelle (University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA) ,  Thiffault Isabelle (Center for Genomic Medicine, Children’s Mercy Research Institute, Kansas City, MO 64108, USA) ,  Thiffault Isabelle (Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, USA) ,  Del Viso Florencia (Center for Genomic Medicine, Children’s Mercy Research Institute, Kansas City, MO 64108, USA) ,  Del Viso Florencia (Department of Pathology and Laboratory Medicine, Children’s Mercy Hospital, Kansas City, MO 64108, USA) ,  Devine Patrick (Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA) ,  Rego Shannon (Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA) ,  Tenney Jessica (Division of Medical Genetics, Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA) ,  van Haeringen Arie (Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, the Netherlands) ,  Ruivenkamp Claudia A.L. (Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, the Netherlands) ,  Koene Saskia (Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, the Netherlands) ,  Robertson Stephen P. (Department of Women’s and Children’s Health, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand) ,  Deshpande Charulata (Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT, UK) ,  Pfundt Rolph (Department of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands) ,  Verbeek Nienke (Department of Genetics, University Medical Centre Utrecht, 3584 CX Utrecht, the Netherlands) ,  van de Kamp Jiddeke M. (Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Weiss Janneke M.M. (Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Weiss Janneke M.M. (Department of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands) ,  Ruiz Anna (Genetics Laboratory, UDIAT-Centre Diagnostic, Parc Tauli Hospital Universitari, Institut d’Investigacio i Innovacio Parc Tauli I3PT, Universitat Autonoma de Barcelona, 08208 Sabadell, Spain) ,  Gabau Elisabeth (Paediatric Unit, Parc Tauli Hospital Universitari, Institut d’Investigacio i Innovacio Parc Tauli I3PT, Universitat Autonoma de Barcelona, 08208 Sabadell, Barcelona, Spain) ,  Banne Ehud (Kaplan Medical Center, Clalit Health Services, Rehovot 76100, Israel) ,  Pepler Alexander (Praxis fuer Humangenetik Tuebingen, 72076 Tuebingen, Germany) ,  Bottani Armand (Service of Genetic Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland) ,  Laurent Sacha (Department of Genetic Medicine, University Hospitals of Geneva and University of Geneva Medical Faculty, Geneva 1211, Switzerland) ,  Guipponi Michel (Department of Genetic Medicine, University Hospitals of Geneva and University of Geneva Medical Faculty, Geneva 1211, Switzerland) ,  Bijlsma Emilia (Department of Clinical Genetics, Leiden University Medical Center, 2333 Leiden, the Netherlands) ,  Bruel Ange-Line (UMR1231 GAD, Inserm - Universite Bourgogne-Franche Comte, 21078 Dijon, France) ,  Bruel Ange-Line (Centre de Reference Deficiences Intellectuelles de Causes Rares, Dijon Bourgogne University Hospital, 21079 Dijon, France) ,  Sorlin Arthur (Centre de Reference Maladies Rares “Anomalies du developpement et syndromes malformatifs,” Centre de Genetique, FHU-TRANSLAD, Dijon Bourgogne University Hospital, 21079 Dijon, France) ,  Willis Mary (Department of Pediatrics, Naval Medical Center San Diego, San Diego, CA 92134, USA) ,  Powis Zoe (Ambry Genetics, CA 92656, USA) ,  Smol Thomas (Univ. Lille, RADEME EA7364, CHU Lille, Institut de Genetique Medicale, 59000 Lille, France) ,  Vincent-Delorme Catherine (Department of Clinical Genetics, CHU Lille, 59000 Lille, France) ,  Baralle Diana (Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK) ,  Colin Estelle (Service de Genetique Medicale, CHU d’Angers, 49933 Angers, France) ,  Revencu Nicole (Center for Human Genetics, Cliniques Universitaires Saint-Luc, Universite Catholique de Louvain, 1200 Brussels, Belgium) ,  Calpena Eduardo (MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK) ,  Wilkie Andrew O.M. (MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK) ,  Chopra Maya (Rosamund Stone Zander Translational Neuroscience Center, Boston Children’s Hospital, Boston, MA 02115, USA) ,  Cormier-Daire Valerie (Universite de Paris, Department of Clinical Genetics and Reference Centre for Constitutional Bone Diseases, INSERM U1163, Imagine Institute, Necker-Enfants Malades Hospital, AP-HP, 75015 Paris, France) ,  Keren Boris (Genetic Department, APHP, Sorbonne Universite, Pitie-Salpetriere Hospital, 47-83 Boulevard de l’Hopital, 75013 Paris, France) ,  Afenjar Alexandra (CRMR Malformations et Maladies Congenitales du Cervelet et Deficiences Intellectuelles de Causes Rares, Departement de Genetique, Sorbonne Universite, AP-HP, Hopital Trousseau, 75012 Paris, France) ,  Niceta Marcello (Area di Ricerca Genetica e Malattie Rare, Ospedale Pediatrico Bambino Gesu, IRCCS, 00146 Rome, Italy) ,  Terracciano Alessandra (Area di Ricerca Medicina Multimodale di Laboratorio, Ospedale Pediatrico Bambino Gesu, IRCCS, 00146 Rome, Italy) ,  Specchio Nicola (Area di Ricerca Scienze Neurologiche e Medicina Riabilitativa, Ospedale Pediatrico Bambino Gesu, IRCCS, 00163 Rome, Italy) ,  Tartaglia Marco (Area di Ricerca Genetica e Malattie Rare, Ospedale Pediatrico Bambino Gesu, IRCCS, 00146 Rome, Italy) ,  Rio Marlene (Department of Genetics, Necker Enfants Malades Hospital, Paris Descartes-Sorbonne Paris Cite University, 75015 Paris, France) ,  Barcia Giulia (Department of Genetics, Necker Enfants Malades Hospital, Paris Descartes-Sorbonne Paris Cite University, 75015 Paris, France) ,  Rondeau Sophie (Department of Genetics, Necker Enfants Malades Hospital, Paris Descartes-Sorbonne Paris Cite University, 75015 Paris, France) ,  Colson Cindy (CHU Lille, Clinique de Genetique, 59000 Lille, France) ,  Bakkers Jeroen (Hubrecht Institute-KNAW and University Medical Center Utrecht, Uppsalalaan 8, 3584 Utrecht, the Netherlands) ,  Bakkers Jeroen (Department of Pediatric Cardiology, Division of Pediatrics, University Medical Center Utrecht, 3584 Utrecht, the Netherlands) ,  Mace Peter D. (Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand) ,  Bicknell Louise S. (Department of Biochemistry, University of Otago, Dunedin 9016, New Zealand) ,  van Haaften Gijs (Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, 3584 Utrecht, the Netherlands)
資料名： American Journal of Human Genetics  (American Journal of Human Genetics)
巻： 109  号： 4  ページ： 750-758  発行年： 2022年 
JST資料番号： B0360B  ISSN： 0002-9297  資料種別： 逐次刊行物 (A)
記事区分： 短報  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： クロマチンは本質的にヌクレオソームのアレイであり,その各々はヒストン八量体の周りに包まれたDNA二本鎖線維から成る。この組織化は,全ての真核生物におけるDNA複製,DNA転写およびDNA修復のような細胞過程を支持する。ヒトヒストンH4は14の正準ヒストンH4遺伝子によりコードされ,全てヌクレオチドレベルで異なるが,不変蛋白質をコードしている。ここでは,6つのH4遺伝子(H4C3,H4C4,H4C5,H4C6,H4C9,およびH4C11)におけるde novoミスセンス変異体を有する29人の被験者のコホートを,全エキソーム配列決定とマッチメイキングによって同定した。全ての個人は知的障害と運動および/または総発達遅延の神経発達特徴を示し,一方,非神経学的特徴はより可変である。10のアミノ酸は,6つの再発性に影響を受け,すべてH4コアまたはC末端尾部に位置した。これらの変異体クラスターはコアH4球状ドメインの特異的領域にクラスターを形成し,蛋白質-蛋白質相互作用は他のヒストンサブユニットまたはヒストンシャペロンのどちらかで起きる。同定された変異体の機能的帰結をゼブラフィッシュ胚において評価し,異常な一般的発達,欠損頭部器官,および減少した体軸長を示し,報告された障害の因果関係に対する有力な証拠を与えた。多発性発生症候群はクロマチン関連因子と関連するが,ミスセンス含有ヒストン変異体(例えば,H3オンコヒストン)は病原性の主因として最近出現している。本知見は発生症候群におけるH4変異体の広範な関与を確立する。Copyright 2022 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： アミノ酸 ,  DNA【核酸】 ,  *遺伝子 ,  転写【遺伝】 ,  *突然変異体 ,  *ヒストン ,  ヒト ,  サブユニット ,  クラスタ ,  DNA修復 ,  真核生物 ,  ヌクレオソーム ,  ゼブラフィッシュ ,  *ミスセンス突然変異
準シソーラス用語： エクソーム , 【Automatic Indexing@JST】

著者キーワード (6件)： ヒストンH4 ,  ヌクレオソーム ,  神経発達障害 ,  知的障害 ,  小頭症 ,  ゼブラフィッシュ

分類 (2件)： 遺伝子発現  (EC02040Q) ,  分子遺伝学一般  (EC02010J)

タイトルに関連する用語 (7件)： ヒストンH4 ,  遺伝子 ,  再発 ,  変異体 ,  神経発達 ,  症候群 ,  基礎