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J-GLOBAL ID：201702236543552928   整理番号：17A1414852

ギャロウェー・モワット症候群:KEOPS複合体遺伝子の変異は原発性小頭症を伴うネフローゼ症候群を引き起こす

Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly

著者 (120件)： BRAUN Daniela A (Harvard Medical School, Massachusetts, USA) ,  RAO Jia (Harvard Medical School, Massachusetts, USA) ,  SCHAPIRO David (Harvard Medical School, Massachusetts, USA) ,  TAN Weizhen (Harvard Medical School, Massachusetts, USA) ,  JOBST-SCHWAN Tilman (Harvard Medical School, Massachusetts, USA) ,  SCHMIDT Johanna Magdalena (Harvard Medical School, Massachusetts, USA) ,  LAWSON Jennifer A (Harvard Medical School, Massachusetts, USA) ,  ASHRAF Shazia (Harvard Medical School, Massachusetts, USA) ,  HOOGSTRATEN Charlotte A (Harvard Medical School, Massachusetts, USA) ,  LOVRIC Svjetlana (Harvard Medical School, Massachusetts, USA) ,  AIRIK Merlin (Harvard Medical School, Massachusetts, USA) ,  HERMLE Tobias (Harvard Medical School, Massachusetts, USA) ,  SHRIL Shirlee (Harvard Medical School, Massachusetts, USA) ,  WIDMEIER Eugen (Harvard Medical School, Massachusetts, USA) ,  GEE Heon Yung (Harvard Medical School, Massachusetts, USA) ,  CHOI Won-Il (Harvard Medical School, Massachusetts, USA) ,  SADOWSKI Carolin E (Harvard Medical School, Massachusetts, USA) ,  PABST Werner L (Harvard Medical School, Massachusetts, USA) ,  WAREJKO Jillian K (Harvard Medical School, Massachusetts, USA) ,  DAGA Ankana (Harvard Medical School, Massachusetts, USA) ,  HILDEBRANDT Friedhelm (Harvard Medical School, Massachusetts, USA) ,  MOLLET Geraldine (INSERM, Paris, FRA) ,  GRIBOUVAL Olivier (INSERM, Paris, FRA) ,  BOYER Olivia (INSERM, Paris, FRA) ,  MARTIN Gaeelle (INSERM, Paris, FRA) ,  FURLANO Monica (INSERM, Paris, FRA) ,  ANTIGNAC Corinne (INSERM, Paris, FRA) ,  MOLLET Geraldine (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  GRIBOUVAL Olivier (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  BOYER Olivia (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  REVY Patrick (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  BODDAERT Nathalie (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  MARTIN Gaeelle (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  FURLANO Monica (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  ANTIGNAC Corinne (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  DAUGERON Marie-Claire (Inst. for Integrative Biology of the Cell (I2BC), CNRS, Gif-sur-Yvette, FRA) ,  COLLINET Bruno (Inst. for Integrative Biology of the Cell (I2BC), CNRS, Gif-sur-Yvette, FRA) ,  LIGER Dominique (Inst. for Integrative Biology of the Cell (I2BC), CNRS, Gif-sur-Yvette, FRA) ,  BASTA Tamara (Inst. for Integrative Biology of the Cell (I2BC), CNRS, Gif-sur-Yvette, FRA) ,  VAN TILBEURGH Herman (Inst. for Integrative Biology of the Cell (I2BC), CNRS, Gif-sur-Yvette, FRA) ,  BOYER Olivia (Necker Hospital, Paris, FRA) ,  REVY Patrick (INSERM, Paris, FRA) ,  SCHANZE Denny (Univ. Hospital Magdeburg, Magdeburg, DEU) ,  ZENKER Martin (Univ. Hospital Magdeburg, Magdeburg, DEU) ,  ULLMANN Jeremy F P (Boston Children’s Hospital, Massachusetts, USA) ,  TRUGLIO Gessica (Boston Children’s Hospital, Massachusetts, USA) ,  PODURI Annapurna (Boston Children’s Hospital, Massachusetts, USA) ,  ULLMANN Jeremy F P (Harvard Medical School, Massachusetts, USA) ,  PODURI Annapurna (Harvard Medical School, Massachusetts, USA) ,  BODDAERT Nathalie (INSERM, Paris, FRA) ,  BODDAERT Nathalie (Necker Hospital, Paris, FRA) ,  COLLINET Bruno (Sorbonne Univ. UPMC, Paris, FRA) ,  FURLANO Monica (Universitat Autonoma de Barcelona, Barcelona, ESP) ,  GUERRERA I Chiara (Univ. Paris Descartes-Structure Federative de Rech. Necker, Paris, FRA) ,  SANCHEZ-FERRAS Oraly (McGill Univ., Quebec, CAN) ,  BOUCHARD Maxime (McGill Univ., Quebec, CAN) ,  HU Jennifer F (Massachusetts Inst. of Technol., Massachusetts, USA) ,  BOSCHAT Anne-Claire (Univ. Paris Descartes-Sorbonne Paris Cite, Paris, FRA) ,  SANQUER Sylvia (Necker Hospital, Paris, FRA) ,  SANQUER Sylvia (Paris Descartes-Sorbonne Paris Cite Univ., Paris, FRA) ,  MENTEN Bjoern (Ghent Univ. Hospital, Ghent, BEL) ,  VERGULT Sarah (Ghent Univ. Hospital, Ghent, BEL) ,  ROCKER Nina De (Ghent Univ. Hospital, Ghent, BEL) ,  CALLEWAERT Bert (Ghent Univ. Hospital, Ghent, BEL) ,  WIDMEIER Eugen (Univ. Freiburg, Freiburg, DEU) ,  GEE Heon Yung (Yonsei Univ. Coll. of Medicine, Seoul, KOR) ,  MATEJAS Verena (Friedrich-Alexander-Univ. Erlangen-Nuernberg, Erlangen, DEU) ,  SCHARMANN Karin (Max Planck Inst. for Molecular Biomedicine, Muenster, DEU) ,  KIENAST Sandra D (Max Planck Inst. for Molecular Biomedicine, Muenster, DEU) ,  LEIDEL Sebastian A (Max Planck Inst. for Molecular Biomedicine, Muenster, DEU) ,  SCHARMANN Karin (Univ. Muenster, Muenster, DEU) ,  KIENAST Sandra D (Univ. Muenster, Muenster, DEU) ,  LEIDEL Sebastian A (Univ. Muenster, Muenster, DEU) ,  BEHNAM Babak (Iran Univ. Medical Sci. (IUMS), Tehran, IRN) ,  BEHNAM Babak (National Inst. of Health, Maryland, USA) ,  BEESON Brendan (Dep. of Diagnostic Imaging, Princess Margaret and King Edward Memorial Hospitals, Western Australia, AUS) ,  BRUCE Malcolm (Dep. of Diagnostic Imaging, Princess Margaret and King Edward Memorial Hospitals, Western Australia, AUS) ,  BEGTRUP Amber (GeneDx, Maryland, USA) ,  CHO Megan T (GeneDx, Maryland, USA) ,  SCHNUR Rhonda E (GeneDx, Maryland, USA) ,  CH’NG Gaik-Siew (Kuala Lumpur Hospital, Kuala Lumpur, MYS) ,  LIN Shuan-Pei (MacKay Children’s Hospital, Taipei, TWN) ,  LIN Shuan-Pei (MacKay Medical Coll., New Taipei City, TWN) ,  TSAI Jeng-Daw (MacKay Medical Coll., New Taipei City, TWN) ,  CHANG Jui-Hsing (MacKay Children’s Hospital, Taipei, TWN) ,  HSU Chyong-Hsin (MacKay Children’s Hospital, Taipei, TWN) ,  TSAI Jeng-Daw (MacKay Children’s Hospital, Taipei, TWN) ,  CHEN Chao-Huei (Taichung Veterans General Hospital, Taichung, TWN) ,  KE Yu-Yuan (Taichung Veterans General Hospital, Taichung, TWN) ,  GAFFNEY Patrick M (Oklahoma Medical Res. Foundation, Oklahoma, USA) ,  GIPSON Patrick E (Univ. Michigan, Michigan, USA) ,  KARI Jameela A (King Abdulaziz Univ., Jeddah, SAU) ,  KIRALY-BORRI Cathy (Genetic Serv. of Western Australia, Princess Margaret Hospital for Children and King Edward Memorial Hospital for Women, Western Australia, AUS) ,  LAI Wai-ming (Princess Margaret Hospital, Hong Kong, CHN) ,  LEMYRE Emmanuelle (Univ. de Montreal, Quebec, CAN) ,  LITTLEJOHN Rebecca Okashah (Baylor Coll. of Medicine, Texas, USA) ,  ROEDER Elizabeth R (Baylor Coll. of Medicine, Texas, USA) ,  MASRI Amira (Univ. Jordan, Amman, JOR) ,  MOGHTADERI Mastaneh (Tehran Univ. Medical Sci., Tehran, IRN) ,  NAKAMURA Kazuyuki (Yamagata Univ. School of Medicine, Yamagata, JPN) ,  SHIIHARA Takashi (Yamagata Univ. School of Medicine, Yamagata, JPN) ,  OZALTIN Fatih (Hacettepe Univ., Ankara, TUR) ,  TOPALOGLU Rezan (Hacettepe Univ., Ankara, TUR) ,  PRAET Marleen (Ghent Univ. Hospital, Ghent, BEL) ,  PRASAD Chitra (Western Univ., Ontario, CAN) ,  PRYTULA Agnieszka (Ghent Univ. Hospital, Ghent, BEL) ,  RUMP Patrick (Univ. Groningen, Groningen, NLD) ,  SINHA Manish D (Guy’s and St Thomas’ NHS Foundation Trust, London, GBR) ,  SOLIMAN Neveen A (Cairo Univ., Cairo, EGY) ,  SOLIMAN Neveen A (Egyptian Group for Orphan Renal Diseases, Cairo, EGY) ,  SOULAMI Kenza (Ibn Rochd Univ. Hospital, Casablanca, MAR) ,  SWEETSER David A (Massachusetts General Hospital for Children, Massachusetts, USA) ,  WAXLER Jessica L (Massachusetts General Hospital for Children, Massachusetts, USA) ,  TSAI Wen-Hui (Chi Mei Medical Center, Tainan, TWN) ,  TSAI Jeng-Daw (Taipei Medical Univ. Hospital, Taipei, TWN) ,  TSAI Jeng-Daw (Taipei Medical Univ., Taipei, TWN) ,  VESTER Udo (Univ. Hospital Essen, Essen, DEU) ,  VISKOCHIL David H (Univ. Utah School of Medicine, Utah, USA) ,  VATANAVICHARN Nithiwat (Mahidol Univ., Bangkok, THA) ,  WIERENGA Klaas J (Oklahoma Univ. Health Sci. Center (OUHSC), Oklahoma, USA)
資料名： Nature Genetics  (Nature Genetics)
巻： 49  号： 10  ページ： 1529-1538  発行年： 2017年10月 
JST資料番号： W0430A  ISSN： 1061-4036  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： ギャロウェー・モワット症候群(GAMOS)は,小児期発症のネフローゼ症候群(SRNS)と脳奇形を伴う小頭症の両者を特徴とする常染色体劣性遺伝性疾患である。本研究では,32家族37人のGAMOS患者において,KEOPS複合体の4つのサブユニットをコードする遺伝子OSGEP,TP53RK,TPRKB,LAGE3に劣性遺伝性変異を同定した。ゼブラフィッシュおよびマウスでCRISPR-Cas9によるノックアウトを行うと,原発性小頭症のヒト表現型が再現され,早期致死となった。OSGEP,TP53RK,あるいはTPRKBのノックダウンは,いずれも細胞増殖を阻害し,ヒトの変異はそれを救済しなかった。これらの遺伝子のノックダウンはまた,タンパク質への翻訳を阻害し,小胞体ストレスを引き起こし,DNA損傷応答シグナル伝達を活性化させ,最終的にアポトーシスを誘導した。OSGEPまたはTP53RKのノックダウンは,アクチン細胞骨格の異常を誘発し,SRNSの中間表現型であることが実証されているヒト足細胞の遊走速度の低下を導いた。以上のように,われわれはGAMOSの単一遺伝子性の原因を新たに4つ同定し,KEOPSの機能とヒト疾患との関連を明らかにし,想定される病因機序について述べた。Copyright Nature Japan KK 2017

シソーラス用語： *腎臓病 ,  *先天性疾患 ,  *小頭症 ,  ヒト ,  劣性 ,  遺伝 ,  *原因遺伝子 ,  遺伝的変異
準シソーラス用語： 変異 ,  *ギャロウェー・モワット症候群 ,  *劣性遺伝性変異

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

タイトルに関連する用語 (7件)： 症候群 ,  複合体 ,  遺伝子 ,  変異 ,  原発 ,  小頭症 ,  ネフローゼ症候群