Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis

Genki Tohnai; Ryoichi Nakamura; Naoki Atsuta; Masahiro Nakatochi; Naoki Hayashi; Daisuke Ito; Hazuki Watanabe; Hirohisa Watanabe; Masahisa Katsuno; Yuishin Izumi; Akira Taniguchi; Kazuaki Kanai; Mitsuya Morita; Osamu Kano; Satoshi Kuwabara; Masaya Oda; Koji Abe; Masashi Aoki; Ikuko Aiba; Koichi Okamoto; Kouichi Mizoguchi; Tomohiko Ishihara; Akihiro Kawata; Takanori Yokota; Kazuko Hasegawa; Isao Nagano; Ichiro Yabe; Fumiaki Tanaka; Satoshi Kuru; Nobutaka Hattori; Kenji Nakashima; Ryuji Kaji; Gen Sobue; Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)

doi:10.1016/j.neurobiolaging.2021.12.002

Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis

Neurobiol Aging. 2022 May:113:131-136. doi: 10.1016/j.neurobiolaging.2021.12.002. Epub 2021 Dec 11.

Authors

Genki Tohnai¹, Ryoichi Nakamura¹, Naoki Atsuta¹, Masahiro Nakatochi², Naoki Hayashi³, Daisuke Ito⁴, Hazuki Watanabe⁵, Hirohisa Watanabe⁶, Masahisa Katsuno⁴, Yuishin Izumi⁷, Akira Taniguchi⁸, Kazuaki Kanai⁹, Mitsuya Morita¹⁰, Osamu Kano¹¹, Satoshi Kuwabara¹², Masaya Oda¹³, Koji Abe¹⁴, Masashi Aoki¹⁵, Ikuko Aiba¹⁶, Koichi Okamoto¹⁷, Kouichi Mizoguchi¹⁸, Tomohiko Ishihara¹⁹, Akihiro Kawata²⁰, Takanori Yokota²¹, Kazuko Hasegawa²², Isao Nagano²³, Ichiro Yabe²⁴, Fumiaki Tanaka²⁵, Satoshi Kuru²⁶, Nobutaka Hattori²⁷, Kenji Nakashima²⁸, Ryuji Kaji⁷, Gen Sobue²⁹; Japanese Consortium for Amyotrophic Lateral Sclerosis Research (JaCALS)

Affiliations

¹ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Aichi Medical University, Nagakute, Japan.
² Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine.
³ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Neurology, Kariya Toyota General Hospital, kariya, Japan.
⁴ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
⁵ Department of Neurology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Department of Neurology, Japanese Red Cross Nagoya Daiichi Hospital, Nagoya, Japan.
⁶ Brain and Mind Research Center, Nagoya University, Nagoya, Japan; Department of Neurology, Fujita Health University, Toyoake, Japan.
⁷ Department of Neurology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
⁸ Department of Neurology, Mie University Graduate School of Medicine, Tsu, Japan.
⁹ Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Neurology, Fukushima Medical University School of Medicine, Fukushima, Japan.
¹⁰ Division of Neurology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan.
¹¹ Division of Neurology, Department of Internal Medicine, Toho University Faculty of Medicine, Tokyo, Japan.
¹² Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
¹³ Department of Neurology, Vihara Hananosato Hospital, Miyoshi, Japan.
¹⁴ Department of Neurology, Okayama University Graduate School of Medicine, Okayama, Japan.
¹⁵ Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
¹⁶ Department of Neurology, National Hospital Organization Higashinagoya National Hospital, Nagoya, Japan.
¹⁷ Department of Neurology, Geriatrics Research Institute and Hospital, Maebashi, Japan.
¹⁸ Department of Neurology, National Hospital Organization Shizuoka Medical Center, Shizuoka, Japan.
¹⁹ Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.
²⁰ Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan.
²¹ Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
²² Division of Neurology, Sagamihara National Hospital, Sagamihara, Japan.
²³ Department of Neurology, National Hospital Organization Miyagi National Hospital, Watari-gun, Japan.
²⁴ Department of Neurology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
²⁵ Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
²⁶ Department of Neurology, National Hospital Organization Suzuka National Hospital, Mie, Japan.
²⁷ Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
²⁸ Department of Neurology, National Hospital Organization, Matsue Medical Center, Matsue, Japan.
²⁹ Aichi Medical University, Nagakute, Japan; Brain and Mind Research Center, Nagoya University, Nagoya, Japan. Electronic address: sobueg@aichi-med-u.ac.jp.

PMID: 35039179
DOI: 10.1016/j.neurobiolaging.2021.12.002

Abstract

DNAJC7 has recently been identified as an amyotrophic lateral sclerosis (ALS) gene via large-scale exome analysis, and its involvement in ALS is still unclear in various populations. This study aimed to determine the frequencies and characteristics of the DNAJC7 variants in a Japanese ALS cohort. A total of 807 unrelated Japanese patients with sporadic ALS were screened via exome analysis. In total, we detected six rare missense variants and one splice-site variant of the DNAJC7 gene, which are not reported in the Japanese public database. Furthermore, the missense variants are located around the TPR domain, which is important for the function of DNAJC7. The total frequency of the DNAJC7 variants in Japanese ALS patients was estimated at 0.87%. Collectively, these results suggest that variants of DNAJC7 are rare cause of Japanese patients with sporadic ALS.

Keywords: Amyotrophic lateral sclerosis; DNAJC7; Whole-exome sequencing.

MeSH terms

Amyotrophic Lateral Sclerosis* / diagnosis
Amyotrophic Lateral Sclerosis* / genetics
Exome
Genetic Predisposition to Disease / genetics
Heat-Shock Proteins / genetics
Humans
Japan
Molecular Chaperones / genetics
Mutation / genetics

Substances

DNAJC7 protein, human
Heat-Shock Proteins
Molecular Chaperones

Supplementary concepts

Amyotrophic lateral sclerosis 1