Unique genetic background and outcome of non-Caucasian Japanese probands with arrhythmogenic right ventricular dysplasia/cardiomyopathy. 6

• Material Type: 博士論文
• ISSN: 2324-9269
• Title: Unique genetic background and outcome of non-Caucasian Japanese probands with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
• Volume: 5 6
• Author/Editor: WADA, Yuko
• Author Heading: WADA, Yuko
• Publication, Distribution, etc.: Wiley Periodicals, Inc.
• Publication Date: 2017-11
• Publication Date (W3CDTF): 2017-11
• Periodical title: Molecular genetics & genomic medicine
• Degree grantor/type: 滋賀医科大学
• Date Granted: 2017-09-13
• Date Granted (W3CDTF): 2017-09-13
• Dissertation Number: 甲第783号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第783号
• Text Language Code: eng
• Subject Heading: Arrhythmogenic right ventricular dysplasia/cardiomyopathy; genetics; phenotype; prognosis; racial difference
• Target Audience: 一般
• Note (General): Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy mainly caused by desmosomal gene mutation. More than half of Caucasian probands have desmosomal mutations, which lead to earlier onset of ventricular arrhythmias. Among non-Caucasians, the genetic background of ARVD/C probands and its prognostic impact remain unclear.; Methods and results:We genotyped 99 unrelated Japanese ARVD/C probands for plakophilin 2 (PKP2), desmoglein 2 (DSG2), desmoplakin (DSP), and desmocollin 2 (DSC2) between 2005 and 2014. Seventy-five probands who fulfilled "definite" category according to the 2010 Task Force Criteria (TFC) were enrolled and followed up for 6.4 years. Sixty-four percent of probands had desmosomal mutations; DSG2 was predominant (48% of mutations) followed by PKP2 (38%). DSG2 mutations were almost missense, whereas over 90% of PKP2 mutations were truncating mutations. Lethal ventricular arrhythmias (VAs, sustained ventricular tachycardia/fibrillation) occurred in 57% of probands as the first manifestation and 71% at the end of follow-up. Five died during follow-up. Truncating mutation carriers exhibited earlier lethal VAs onset compared to missense mutation carriers or mutation negatives (age at onset 35 ± 12, 49 ± 16, and 50 ± 19 years, respectively, P < 0.05 in each). Cox proportional hazard analysis revealed for the first time that, compared to mutation negatives, truncating mutation carriers had higher risk for lethal VAs, and especially for onset by their 40s, in an age-dependent manner (RR = 4.6, P < 0.01 by their 40s; RR = 2.9, P = 0.01 by their 50s).; Conclusion:The genetic background of Japanese ARVD/C probands is distinct from that of Caucasian probands, leading to distinct prognosis. The most affected gene mutations in Japanese probands were missense mutations in DSG2 leading to modest outcome, whereas PKP2 truncating mutations were the second most and might be a strong marker for lethal VAs in non-Caucasian Japanese ARVD/C probands.; Thesis or Dissertation; 平成29年度; 10.1002/mgg3.311
• DOI: info:doi/10.1002/mgg3.311; https://doi.org/info:doi/10.1002/mgg3.311
• Persistent ID (NDL): info:ndljp/pid/11099599; https://dl.ndl.go.jp/pid/11099599
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2018-06-04T01:14:06+09:00
• Date Created (W3CDTF): 2018-04-12
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10422/00012404; https://shiga-med.repo.nii.ac.jp/records/3266
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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