文献

J-GLOBAL ID：201902253030717725   整理番号：19A2206353

小脳奇形の病因景観の再定義【JST・京大機械翻訳】

Redefining the Etiologic Landscape of Cerebellar Malformations

著者 (61件)： Aldinger Kimberly A. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Timms Andrew E. (Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Thomson Zachary (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Mirzaa Ghayda M. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Mirzaa Ghayda M. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Bennett James T. (Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Bennett James T. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Rosenberg Alexander B. (Department of Electrical Engineering, University of Washington, Seattle, WA 98105, USA) ,  Roco Charles M. (Department of Bioengineering, University of Washington, Seattle, WA 98105, USA) ,  Hirano Matthew (Department of Electrical Engineering, University of Washington, Seattle, WA 98105, USA) ,  Abidi Fatima (Greenwood Genetic Center, Greenwood, SC 29646, USA) ,  Haldipur Parthiv (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Cheng Chi V. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Collins Sarah (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Park Kaylee (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Zeiger Jordan (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Overmann Lynne M. (Institute of Genetic Medicine, Newcastle University, International Centre for life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK) ,  Alkuraya Fowzan S. (Department of Genetics, King Faisal Specialist Hospital Research Center, Riyadh, 11211, Saudi Arabia) ,  Biesecker Leslie G. (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892 USA) ,  Braddock Stephen R. (Department of Pediatrics, Saint Louis University School of Medicine, St. Louis, MO 63104, USA) ,  Cathey Sara (Greenwood Genetic Center, Greenwood, SC 29646, USA) ,  Cho Megan T. (GeneDx, Gaithersburg, MD 20877, USA) ,  Chung Brian H.Y. (Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China) ,  Everman David B. (Greenwood Genetic Center, Greenwood, SC 29646, USA) ,  Zarate Yuri A. (Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, AR, 72202, USA) ,  Jones Julie R. (Greenwood Genetic Center, Greenwood, SC 29646, USA) ,  Schwartz Charles E. (Greenwood Genetic Center, Greenwood, SC 29646, USA) ,  Goldstein Amy (Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA) ,  Goldstein Amy (The Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA) ,  Hopkin Robert J. (Division of Human Genetics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA) ,  Krantz Ian D. (The Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA) ,  Krantz Ian D. (Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104 USA) ,  Ladda Roger L. (Department of Pediatrics, Milton S Hershey Medical Center, Hershey, PA 17033, USA) ,  Ladda Roger L. (Departments of Pathology, Milton S Hershey Medical Center, Hershey, PA 17033, USA) ,  Leppig Kathleen A. (Genetic Services, Kaiser Permanente Washington, Seattle, WA 98112, USA) ,  McGillivray Barbara C. (Department of Medical Genetics, Children’s and Women’s Health Centre of British Columbia, Vancouver, BC V6H 3N1, Canada) ,  Sell Susan (Department of Pediatrics, Milton S Hershey Medical Center, Hershey, PA 17033, USA) ,  Wusik Katherine (Division of Human Genetics, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA) ,  Gleeson Joseph G. (Department of Neurosciences, Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA) ,  Nickerson Deborah A. (Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA) ,  Nickerson Deborah A. (University of Washington Center for Mendelian Genomics, Seattle, WA 98195, USA) ,  Bamshad Michael J. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Bamshad Michael J. (Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA) ,  Bamshad Michael J. (University of Washington Center for Mendelian Genomics, Seattle, WA 98195, USA) ,  Gerrelli Dianne (University College London Institute of Child Health, London WC1N 1EH, UK) ,  Lisgo Steven N. (Institute of Genetic Medicine, Newcastle University, International Centre for life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK) ,  Seelig Georg (Department of Electrical Engineering, University of Washington, Seattle, WA 98105, USA) ,  Seelig Georg (Paul G. Allen School of Computer Science & Engineering, University of Washington, Seattle, WA 98195, USA) ,  Ishak Gisele E. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Ishak Gisele E. (Department of Radiology, University of Washington, Seattle, WA 98195, USA) ,  Barkovich A. James (Departments of Radiology, Neurology, Pediatrics, and Neurosurgery, University of California, San Francisco, San Francisco, CA 94143, USA) ,  Curry Cynthia J. (Genetic Medicine, Department of Pediatrics, University of California San Francisco, Fresno, CA, 93701, USA) ,  Glass Ian A. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Glass Ian A. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Millen Kathleen J. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Millen Kathleen J. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Doherty Dan (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Doherty Dan (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Dobyns William B. (Center for Integrative Brain Research, Seattle Children’s Research Institute, Seattle, WA 98101, USA) ,  Dobyns William B. (Department of Pediatrics, University of Washington, Seattle, WA 98105, USA) ,  Dobyns William B. (Department of Neurology, University of Washington, Seattle, WA 98105, USA)
資料名： American Journal of Human Genetics  (American Journal of Human Genetics)
巻： 105  号： 3  ページ： 606-615  発行年： 2019年 
JST資料番号： B0360B  ISSN： 0002-9297  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 小脳奇形は発生障害としばしば関連する多様な先天異常である。遺伝的および出生前の非遺伝的原因が記述されているが,系統的な分析は行われていない。ここでは,Dandy-Walker奇形(DWM)と小脳低形成(CBLH)の大規模な配列決定研究を提示する。DWMまたはCBLHを有する100家族から282人においてexome配列を行い,100家族のうち36人において分子診断を確立し,DWM(16%)よりもCBLH(51%)に対して有意に高い収率を示した。41の変異体は27の神経発達障害関連遺伝子に影響を及ぼし,CBLHとDWMはしばしば単核性神経発達障害の特徴であることを示した。7つの単遺伝子性原因(19%)のみが1つ以上の個体で同定されたが,131の追加個体の神経画像レビューは27の遺伝的疾患(85%)の23において小脳異常を確認した。出生前リスク因子は,遺伝子診断のない個人(64人のうち30人[47%])の間で頻繁に見出された。出生前ヒト小脳組織の単一細胞RNA配列決定は,ニューロンおよび血管細胞型における遺伝子濃縮を明らかにした;これは,欠損血管形成が小脳発達を破壊することを示唆する。さらに,血管前駆体シグナル伝達に必須のチロシンキナーゼ受容体,PDGFRBにおけるde novo獲得機能変異体はCBLHと関連しており,この発見は遺伝的および非遺伝的病因を結びつけている。我々の結果は,遺伝的欠損が特異的な小脳細胞型に影響し,小脳奇形の機構として異常な血管発生を暗示することを示唆する。著者らはまた,小脳異常を有する個人における非遺伝的出生前因子に対する主要な寄与を確認し,再発リスクと予後に関する診断評価とカウンセリングに実質的に影響を及ぼしている。Copyright 2019 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： *小脳 ,  遺伝子 ,  遺伝 ,  ヒト ,  細胞情報伝達 ,  血管 ,  てんかん ,  RNA【核酸】 ,  遺伝子診断 ,  ニューロン ,  *病因 ,  危険因子 ,  予後
準シソーラス用語： 出生 ,  *脳奇形 , 【Automatic Indexing@JST】

著者キーワード (10件)： 自閉症 ,  小脳形成不全 ,  小脳 ,  Dandy-Walker奇形 ,  てんかん ,  エクソーム ,  遺伝子 ,  ヘテロトピア ,  知的障害 ,  双生児

分類 (2件)： 遺伝的変異  (EC01030Y) ,  先天性疾患・奇形一般  (GD03010V)

タイトルに関連する用語 (3件)： 脳奇形 ,  病因 ,  景観