日本におけるCharcot-Marie-Tooth病患者1,005人の遺伝的プロファイルと発症特性

• Material Type: 博士論文
• Title: 日本におけるCharcot-Marie-Tooth病患者1,005人の遺伝的プロファイルと発症特性
• Volume: 90 2
• Author/Editor: 吉村, 明子
• Author Heading: 吉村, 明子
• Publication, Distribution, etc.: 鹿児島大学
• Publication Date: 2019; 90 2
• Publication Date (W3CDTF): 2019
• Alternative Title: Genetic Profile and Onset Features of 1,005 Patients with Charcot-Marie-Tooth disease in Japan
• Periodical title: Journal of Neurology, Neurosurgery & Psychiatry
• Degree grantor/type: 鹿児島大学
• Date Granted: 2019-01-20
• Date Granted (W3CDTF): 2019-01-20
• Dissertation Number: 甲総研第490号
• Degree Type: 博士(医学); Doctor of Philosophy in Medical Science
• Conferring No. (Dissertation): 甲総研第490号
• Text Language Code: eng
• Subject Heading: Charcot-Marie-Tooth disease; Molecular epidemiology; next generation sequencing; Gene panel
• NDC: 492
• Target Audience: 一般
• Note (General): 博士論文本文, 最終試験結果の要旨, 論文審査の要旨, 博士論文要旨; Objective: To identify the genetic characteristics in a large-scale of patients with Charcot-Marie-Tooth disease (CMT) patients.Methods: From May 2012 to August 2016, we collected 1005 cases with suspected CMT throughout Japan, whereas PMP22 duplication/deletion were excluded in advance for demyelinating CMT cases. We performed next generation sequencing targeting CMT-related gene panels using Illumina MiSeq or Ion Proton, then analyzed the gene-specific onset age of the identified cases and geographical differences in terms of their genetic spectrum.Results: From 40 genes, we identified pathogenic or likely pathogenic variants in 301 cases (30.0%). The most common causative genes were GJB1 (n = 66, 21.9%), MFN2 (n = 66, 21.9%), and MPZ (n = 51, 16.9%). In demyelinating CMT, variants were detected in 45.7% cases, and the most common reasons were GJB1 (40.3%), MPZ (27.1%), PMP22 point mutations (6.2%), and NEFL (4.7%). Axonal CMT yielded a relatively lower detection rate (22.9%), and the leading causes, occupying 72.4%, were MFN2 (37.2%), MPZ (9.0%), HSPB1 (8.3%), GJB1 (7.7%), GDAP1 (5.1%), and MME (5.1%). First decade of life was found as the most common disease onset period, and early-onset CMT cases were most likely to receive a molecular 1 diagnosis. Geographical distribution analysis indicated distinctive genetic spectrums in different regions of Japan.Conclusions: Our results updated the genetic profile within a large-scale of Japanese CMT cases. Subsequent analyses regarding onset age and geographical distribution advanced our understanding of CMT, which would be beneficial for clinicians.This article has been accepted for publication in Journal of Neurology, Neurosurgery & Psychiatry, 2019 following peer review, and the Version of Record can be accessed online at http://dx.doi.org/10.1136/jnnp-2018-318839.
• DOI: info:doi/10.1136/jnnp-2018-318839; https://doi.org/info:doi/10.1136/jnnp-2018-318839
• Persistent ID (NDL): info:ndljp/pid/11246037; https://dl.ndl.go.jp/pid/11246037
• 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): 2019-03-03T03:58:25+09:00
• Date Created (W3CDTF): 2019-01-28
• Format (IMT): PDF; 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
• Original Material (URI): https://jnnp.bmj.com/
• Periodical Title (URI): http://hdl.handle.net/10232/00030434
• 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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