Genetic and clinical study of in Japanese Parkinson's disease.

Background: Biallelic variants in , which encodes protein-nucleic acid deglycase DJ-1, can cause early-onset Parkinson's disease (PD). Although many patients with 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 variants in Japan.

Methods: We performed a molecular genetic analysis of PD patients with 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 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 variants. We identified a relatively low frequency of 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 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.