Genetic profile and onset features of 1005 patients with Charcot-Marie-Tooth disease in Japan

DOI Web Site PubMed 被引用文献16件 参考文献27件 オープンアクセス

書誌事項

公開日
2018-09-26
資源種別
journal article
DOI
  • 10.1136/jnnp-2018-318839
公開者
BMJ

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説明

<jats:sec><jats:title>Objective </jats:title><jats:p>To identify the genetic characteristics in a large-scale of patients with Charcot-Marie-Tooth disease (CMT).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>From May 2012 to August 2016, we collected 1005 cases with suspected CMT throughout Japan, whereas <jats:italic>PMP22</jats:italic> 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 analysed the gene-specific onset age of the identified cases and geographical differences in terms of their genetic spectrum.</jats:p></jats:sec><jats:sec><jats:title>Results </jats:title><jats:p>From 40 genes, we identified pathogenic or likely pathogenic variants in 301 cases (30.0%). The most common causative genes were <jats:italic>GJB1</jats:italic> (n=66, 21.9%), <jats:italic>MFN2</jats:italic> (n=66, 21.9%) and <jats:italic>MPZ</jats:italic> (n=51, 16.9%). In demyelinating CMT, variants were detected in 45.7% cases, and the most common reasons were <jats:italic>GJB1</jats:italic> (40.3%), <jats:italic>MPZ</jats:italic> (27.1%), <jats:italic>PMP22</jats:italic> point mutations (6.2%) and <jats:italic>NEFL</jats:italic> (4.7%). Axonal CMT yielded a relatively lower detection rate (22.9%), and the leading causes, occupying 72.4%, were <jats:italic>MFN2</jats:italic> (37.2%), <jats:italic>MPZ</jats:italic> (9.0%), <jats:italic>HSPB1</jats:italic> (8.3%), <jats:italic>GJB1</jats:italic> (7.7%), <jats:italic>GDAP1</jats:italic> (5.1%) and <jats:italic>MME</jats:italic> (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 diagnosis. Geographical distribution analysis indicated distinctive genetic spectrums in different regions of Japan.</jats:p></jats:sec><jats:sec><jats:title>Conclusions </jats:title><jats:p>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.</jats:p></jats:sec>

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