ABSTRACT
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.
