npj Genomic Medicine (Oct 2022)
Rapid and comprehensive diagnostic method for repeat expansion diseases using nanopore sequencing
- Satoko Miyatake,
- Eriko Koshimizu,
- Atsushi Fujita,
- Hiroshi Doi,
- Masaki Okubo,
- Taishi Wada,
- Kohei Hamanaka,
- Naohisa Ueda,
- Hitaru Kishida,
- Gaku Minase,
- Atsuhiro Matsuno,
- Minori Kodaira,
- Katsuhisa Ogata,
- Rumiko Kato,
- Atsuhiko Sugiyama,
- Ayako Sasaki,
- Takabumi Miyama,
- Mai Satoh,
- Yuri Uchiyama,
- Naomi Tsuchida,
- Haruka Hamanoue,
- Kazuharu Misawa,
- Kiyoshi Hayasaka,
- Yoshiki Sekijima,
- Hiroaki Adachi,
- Kunihiro Yoshida,
- Fumiaki Tanaka,
- Takeshi Mizuguchi,
- Naomichi Matsumoto
Affiliations
- Satoko Miyatake
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Eriko Koshimizu
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Atsushi Fujita
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Hiroshi Doi
- Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine
- Masaki Okubo
- Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine
- Taishi Wada
- Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine
- Kohei Hamanaka
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Naohisa Ueda
- Department of Neurology, Yokohama City University Medical Center
- Hitaru Kishida
- Department of Neurology, Yokohama City University Medical Center
- Gaku Minase
- Department of Obstetrics and Gynecology, Asahikawa Medical University
- Atsuhiro Matsuno
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
- Minori Kodaira
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
- Katsuhisa Ogata
- Department of Neurology, National Hospital Organization Higashisaitama National Hospital
- Rumiko Kato
- Department of Pediatrics, National Hospital Organization Higashisaitama National Hospital
- Atsuhiko Sugiyama
- Department of Neurology, Graduate School of Medicine, Chiba University
- Ayako Sasaki
- Department of Pediatrics, Yamagata University School of Medicine
- Takabumi Miyama
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Mai Satoh
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Yuri Uchiyama
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Naomi Tsuchida
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Haruka Hamanoue
- Department of Clinical Genetics, Yokohama City University Hospital
- Kazuharu Misawa
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Kiyoshi Hayasaka
- Department of Pediatrics, Yamagata University School of Medicine
- Yoshiki Sekijima
- Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine
- Hiroaki Adachi
- Department of Neurology, University of Occupational and Environmental Health School of Medicine
- Kunihiro Yoshida
- Department of Neurology, JA Nagano Kouseiren, Kakeyu-Misayama Rehabilitation Center, Kakeyu Hospital
- Fumiaki Tanaka
- Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine
- Takeshi Mizuguchi
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- Naomichi Matsumoto
- Department of Human Genetics, Yokohama City University Graduate School of Medicine
- DOI
- https://doi.org/10.1038/s41525-022-00331-y
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 15
Abstract
Abstract We developed a diagnostic method for repeat expansion diseases using a long-read sequencer to improve currently available, low throughput diagnostic methods. We employed the real-time target enrichment system of the nanopore GridION sequencer using the adaptive sampling option, in which software-based target assignment is available without prior sample enrichment, and built an analysis pipeline that prioritized the disease-causing loci. Twenty-two patients with various neurological and neuromuscular diseases, including 12 with genetically diagnosed repeat expansion diseases and 10 manifesting cerebellar ataxia, but without genetic diagnosis, were analyzed. We first sequenced the 12 molecularly diagnosed patients and accurately confirmed expanded repeats in all with uniform depth of coverage across the loci. Next, we applied our method and a conventional method to 10 molecularly undiagnosed patients. Our method corrected inaccurate diagnoses of two patients by the conventional method. Our method is superior to conventional diagnostic methods in terms of speed, accuracy, and comprehensiveness.
