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J-GLOBAL ID：202002291894914030   整理番号：20A1827209

Slavic諸国におけるc.256257delAA創始者変異体を含むRAG欠損患者82名の臨床および遺伝子スペクトル【JST・京大機械翻訳】

The Clinical and Genetic Spectrum of 82 Patients With RAG Deficiency Including a c.256_257delAA Founder Variant in Slavic Countries

著者 (65件)： Sharapova Svetlana O. (Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, Belarus) ,  Skomska-Pawliszak Malgorzata (Department of Immunology, Children’s Memorial Health Institute, Warsaw, Poland) ,  Rodina Yulia A. (Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Wolska-Kusnierz Beata (Department of Immunology, Children’s Memorial Health Institute, Warsaw, Poland) ,  Dabrowska-Leonik Nel (Department of Immunology, Children’s Memorial Health Institute, Warsaw, Poland) ,  Mikoluc Bozena (Department of Pediatrics, Rheumatology, Immunology and Metabolic Bone Diseases, Medical University of Bialystok, Bialystok, Poland) ,  Pashchenko Olga E. (Immunology Department, Pirogov Russian National Research Medical University, Moscow, Russia) ,  Pasic Srdjan (Pediatric Immunology, Medical Faculty, Mother and Child Health Institute, University of Belgrade, Belgrade, Serbia) ,  Freiberger Tomas (Centre for Cardiovascular Surgery and Transplantation, Brno, Czechia) ,  Freiberger Tomas (Faculty of Medicine, Masaryk University, Brno, Czechia) ,  Milota Tomas (Department of Immunology, University Hospital Motol, Prague, Czechia) ,  Milota Tomas (Second Faculty of Medicine, Charles University, Prague, Czechia) ,  Formankova Renata (Department of Pediatric Hematology and Oncology, University Hospital Motol, Prague, Czechia) ,  Formankova Renata (Faculty of Medicine, Charles University, Prague, Czechia) ,  Szaflarska Anna (Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland) ,  Siedlar Maciej (Department of Clinical Immunology, Institute of Pediatrics, Jagiellonian University Medical College, Krakow, Poland) ,  Siedlar Maciej (Department of Clinical Immunology, University Children’s Hospital, Krakow, Poland) ,  Avcin Tadej (University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia) ,  Avcin Tadej (Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia) ,  Markelj Gasper (University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia) ,  Markelj Gasper (Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia) ,  Ciznar Peter (Pediatric Department, Faculty of Medicine, Comenius University, Bratislava, Slovakia) ,  Kalwak Krzysztof (Department of Pediatric Hematology/Oncology and BMT, Wroclaw Medical University, Wroclaw, Poland) ,  Koltan Sylwia (Department of Pediatrics, Hematology and Oncology Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland) ,  Koltan Sylwia (Nicolaus Copernicus University in Torun, Torun, Poland) ,  Jackowska Teresa (Department of Pediatrics, Medical Center of Postgraduate Education, Warsaw, Poland) ,  Drabko Katarzyna (Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, Lublin, Poland) ,  Gagro Alenka (Department of Pediatrics, School of Medicine, Zagreb Children’s Hospital, University of Zagreb, Zagreb, Croatia) ,  Gagro Alenka (Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia) ,  Pac Malgorzata (Department of Immunology, Children’s Memorial Health Institute, Warsaw, Poland) ,  Naumova Elissaveta (Department of Clinical Immunology, University Hospital Alexandrovska, Sofia, Bulgaria) ,  Kandilarova Snezhina (Department of Clinical Immunology, University Hospital Alexandrovska, Sofia, Bulgaria) ,  Babol-Pokora Katarzyna (Department of Pediatrics, Oncology and Hematology, Medical University of Lodz, Lodz, Poland) ,  Varabyou Dzmitry S. (Department of Geographical Ecology, Belarusian State University, Minsk, Belarus) ,  Barendregt Barbara H. (Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands) ,  Raykina Elena V. (Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Varlamova Tatiana V. (Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Pavlova Anna V. (Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Grombirikova Hana (Centre for Cardiovascular Surgery and Transplantation, Brno, Czechia) ,  Grombirikova Hana (Faculty of Medicine, Masaryk University, Brno, Czechia) ,  Debeljak Marusa (University Children’s Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia) ,  Debeljak Marusa (Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia) ,  Mersiyanova Irina V. (Laboratory of Molecular Biology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Bondarenko Anastasiia V. (Department of Pediatric Infectious Diseases and Pediatric Immunology, Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine) ,  Chernyshova Liudmyla I. (Department of Pediatric Infectious Diseases and Pediatric Immunology, Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine) ,  Kostyuchenko Larysa V. (Pediatric Department, West-Ukrainian Specialized Children’s Medical Center, Lviv, Ukraine) ,  Guseva Marina N. (Consulting Center of Pediatric Medical Academy, St. Petersburg, Russia) ,  Rascon Jelena (Center for Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania) ,  Muleviciene Audrone (Center for Pediatric Oncology and Hematology, Vilnius University, Vilnius, Lithuania) ,  Preiksaitiene Egle (Hematology, Oncology and Transfusion Medicine Center, Vilnius University, Vilnius, Lithuania) ,  Geier Christoph B. (Immunology Outpatient Clinic, Vienna, Austria) ,  Leiss-Piller Alexander (Immunology Outpatient Clinic, Vienna, Austria) ,  Yamazaki Yasuhiro (Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States) ,  Kawai Tomoki (Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States) ,  Walter Jolan E. (University of South Florida at Johns Hopkins All Children’s Hospital, Saint Petersburg, FL, United States) ,  Walter Jolan E. (Massachusetts General Hospital for Children, Boston, MA, United States) ,  Kondratenko Irina V. (Department of Clinical Immunology, Russian Clinical Children’s Hospital by Pirogov Russian National Research Medical University, Moscow, Russia) ,  Sediva Anna (Department of Immunology, University Hospital Motol, Prague, Czechia) ,  Sediva Anna (Second Faculty of Medicine, Charles University, Prague, Czechia) ,  van der Burg Mirjam (Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands) ,  van der Burg Mirjam (Department of Pediatric, Laboratory for Pediatric Immunology, Willem Alexander Children’s Hospital, LUMC, Leiden, Netherlands) ,  Kuzmenko Natalia B. (Department of Epidemiology and Monitoring of Primary Immunodeficiencies, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia) ,  Notarangelo Luigi D. (Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States) ,  Bernatowska Ewa (Department of Immunology, Children’s Memorial Health Institute, Warsaw, Poland) ,  Aleinikova Olga V. (Research Department, Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk Region, Belarus)
資料名： Frontiers in Immunology (Web)  (Frontiers in Immunology (Web))
巻： 11  ページ： 900  発行年： 2020年 
JST資料番号： U7074A  ISSN： 1664-3224  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： スイス (CHE)  言語： 英語 (EN)

抄録/ポイント： 背景:組換え活性化遺伝子(RAG)の変異は,重症複合免疫不全(SCID),Omenn症候群(OS),漏出性SCID,および肉芽腫および/または自己免疫(CID-G/AI)とのCID,および抗体欠損を伴う軽度な提示から,複合免疫欠損症(CID)の常染色体劣性型の一般的遺伝的原因である。目的:著者らは,南,西,および東Slavic諸国に住む集団におけるRAG欠損患者の地理的分布による発生率,臨床症状,遺伝的変異,および治療転帰を推定することを目的とする。方法:人口統計学的,臨床的および臨床検査データを,チャートレビューを介し,Slavic起源のRAG欠損患者から採取した。レコンビナーゼ活性をフローサイトメトリーに基づくアッセイによってin vitroで測定した。結果:臨床的および免疫学的表現型に基づき,68家族からの82人の患者のコホートは,SCID(n=20),OS(n=37)およびLS/CID(n=25)表現型を含む,RAG欠損の広域スペクトルを示した。67例(81.7%)の患者がRAG1と15例の患者(18.3%)がRAG2バイ対立遺伝子変異体を持っていた。Slavic諸国におけるRAG欠損の最小年間発生率は180,000と300,000の生児出生で1の間で変化し,これらの地域の健康管理格差に二次的に変化する可能性があると見積もる。本コホートでは,RAG1変異体の70%(n=47)は,ホモ接合(n=18,27%)または複合ヘテロ接合(n=29,43%)型のどちらかで,p.K86Vfs*33(c.256257delAA)対立遺伝子を持っていた。ホモ接合RAG1 p.K86Vfs*33変異体の大多数(77%)は中央および東部ポーランドのVistula流域地域に由来し,化合物ヘテロ接合体症例はBulgariaを除く全てのSlavic諸国に分布した。ホモ接合RAG1 p.K86Vfs*33症例の臨床的および免疫学的提示は,最終表現型形成における付加的遺伝的および/またはエピジェネティック因子の強い影響を示唆する高度に多様であった(SCID,OSおよびAS/CID)。結論:RAG1 p.K86Vfs*33はポーランドのVistula流域地域に由来する創始者変異体であり,中央および東部ポーランドからのホモ接合症例の割合が高く,全てのSlavsにおける変異体の存在を説明する可能性がある。RAG1創始者変異体のこのコホートでの我々の研究は,臨床的および免疫学的表現型が,部分的には遺伝的欠損の基になることを確認した。HSCTへのアクセスは,東ヨーロッパのRAG欠損患者の間で改善し,生存の改善を予想する。Copyright 2020 The Author(s) All rights reserved. Translated from English into Japanese by JST.【JST・京大機械翻訳】

シソーラス用語： ヘテロ接合 ,  *遺伝 ,  *遺伝子 ,  抗体 ,  表現型 ,  自己免疫 ,  対立遺伝子 ,  健康管理 ,  母集団 ,  フローサイトメトリー ,  常染色体 ,  免疫不全症候群 ,  in vitro実験 ,  エピジェネティクス
準シソーラス用語： RAG1 , 【Automatic Indexing@JST】

著者キーワード (6件)： RAG1 ,  RAG2 ,  原発性免疫不全 ,  地理的分布 ,  発生率 ,  Slavic小児

分類 (1件)： 免疫性疾患・アレルギー性疾患一般  (GD04010C)

引用文献 (40件)：

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タイトルに関連する用語 (7件)： 変異体 ,  RAG ,  欠損 ,  患者 ,  臨床 ,  遺伝子 ,  スペクトル