Genetic and clinical study of PARK7 in Japanese Parkinson's disease
Mayu Ishiguro,
Manabu Funayama,
Taku Hatano,
Hiroshi Nishida,
Yuko Wada,
Kazuyuki Noda,
Masahiko Tomiyama,
Hiroyo Yoshino,
Yuanzhe Li,
Stephanie Ong,
Ettore Cioffi,
Kenya Nishioka,
Nobutaka Hattori
Affiliations
Mayu Ishiguro
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan
Manabu Funayama
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan; International Collaborative Research Administration, Juntendo University, Tokyo, Japan; Corresponding author. Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Taku Hatano
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan
Hiroshi Nishida
Department of Neurology, Gifu Prefectural General Medical Center, Gifu, Japan
Yuko Wada
Department of Neurology, Rakuwa-kai Otowa Hospital, Kyoto, Japan
Kazuyuki Noda
Department of Neurology, Juntendo University Shizuoka Hospital, Shizuoka, Japan
Masahiko Tomiyama
Department of Neurology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
Hiroyo Yoshino
Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan
Yuanzhe Li
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan; Department of Diagnosis, Prevention and Treatment of Dementia, Graduate School of Medicine, Juntendo University, Tokyo, Japan
Stephanie Ong
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan; International Collaborative Research Administration, Juntendo University, Tokyo, Japan
Ettore Cioffi
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan
Kenya Nishioka
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan; Department of Neurology, Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan
Nobutaka Hattori
Department of Neurology, Faculty of Medicine, Juntendo University, Tokyo, Japan; Research Institute for Diseases of Old Age, Graduate School of Medicine, Juntendo University, Tokyo, Japan; International Collaborative Research Administration, Juntendo University, Tokyo, Japan; Department of Diagnosis, Prevention and Treatment of Dementia, Graduate School of Medicine, Juntendo University, Tokyo, Japan; Neurodegenerative Disorders Collaborative Laboratory, RIKEN Center for Brain Science, Saitama, Japan; Corresponding author. Department of Neurology, Faculty of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Background: Biallelic variants in PARK7, which encodes protein-nucleic acid deglycase DJ-1, can cause early-onset Parkinson's disease (PD). Although many patients with PARK7 variants have been identified from European and Middle Eastern ethnic groups, there have been no reports in the Japanese population. Objectives: To determine the prevalence and clinical features of patients with PD harboring PARK7 variants in Japan. Methods: We performed a molecular genetic analysis of PD patients with PARK7 variants identified using comprehensive panel sequencing, to explore the details of variants. Moreover, clinical neurological features were investigated, including neuroimaging analyses. This study followed STROBE guidelines. Results: Four patients with biallelic rare variants of PARK7 were identified in the cohort. All four patients presented with levodopa-responsive parkinsonism, with an age at onset in the early 30s. Furthermore, two of the four patients had psychiatric complications. Dopamine transporter imaging revealed nigrostriatal pathway dysfunction. Conclusions: To our knowledge, this is the first report of Japanese patients with PARK7 variants. We identified a relatively low frequency of PARK7 variants in patients in Japan. As opposed to typical patients with sporadic PD, the identified patients developed the disease in their 30s and presented with a variety of non-motor symptoms and complications. Further studies are needed to identify the clinical features related to PARK7 variants in Japanese patients with PD, and to analyze the pathophysiology of how the variants identified in the present study might affect DJ-1 function.
