並列タイトル等Complex hereditary peripheral neuropathies caused by novel variants in mitochondrial-related nuclear genes
学位博士(医学)
Doctor of Philosophy in Medical Science
一般注記博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨
Mitochondrial disorders are a group of clinically and genetically heterogeneous multisystem disorders and peripheral neuropathy is frequently described in the context of mutations in mitochondrial-related nuclear genes. This study aimed to identify the causative mutations in mitochondrial-related nuclear genes in suspected hereditary peripheral neuropathy patients. We enrolled a large Japanese cohort of clinically suspected hereditary peripheral neuropathy patients who were mutation negative in the prescreening of the known Charcot–Marie–Tooth disease-causing genes. We performed whole-exome sequencing on 247 patients with autosomal recessive or sporadic inheritance for further analysis of 167 mitochondrial-related nuclear genes. We detected novel bi-allelic likely pathogenic/pathogenic variants in four patients, from four mitochondrial-related nuclear genes: pyruvate dehydrogenase beta-polypeptide (PDHB), mitochondrial poly(A) polymerase (MTPAP), hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase, beta subunit (HADHB), and succinate-CoA ligase ADP-forming beta subunit (SUCLA2). All these patients showed sensory and motor axonal polyneuropathy, combined with central nervous system or multisystem involvements. The pathological analysis of skeletal muscles revealed mild neurogenic changes without significant mitochondrial abnormalities. Targeted screening of mitochondria-related nuclear genes should be considered for patients with complex hereditary axonal polyneuropathy, accompanied by central nervous system dysfunctions, or with unexplainable multisystem disorders.
Yu Hiramatsu, Yuji Okamoto, Akiko Yoshimura, Jun-Hui Yuan, Masahiro Ando, Yujiro Higuchi, Akihiro Hashiguchi, Eiji Matsuura, Fumihito Nozaki, Tomohiro Kumada, Kei Murayama, Mikiya Suzuki, Yuki Yamamoto, Naoko Matsui, Yoshimichi Miyazaki, Masamitsu Yamaguchi, Youji Suzuki, Jun Mitsui, Hiroyuki Ishiura, Masaki Tanaka, Shinichi Morishita, Ichizo Nishino, Shoji Tsuji & Hiroshi Takashima
Complex hereditary peripheral neuropathies caused by novel variants in mitochondrial-related nuclear genes
Journal of Neurology (2022) 269:4129–4140
The version of record of this article, first published in Journal of Neurology, is available online at Publisher’s website: https://doi.org/10.1007/s00415-022-11026-w
連携機関・データベース国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）