Non-coding repeat analyses in patients with Parkinson's disease.

INTRODUCTION

The genetic etiology of Parkinson's disease (PD) is complex; approximately 10% of patients with PD have various gene mutations that lead to familial forms of the disease. Recent analyses of non-coding repeat regions revealed that many neurodegenerative diseases are associated with pathological expansions. We evaluated the genetic background of non-coding repeat expansions in Japanese patients with PD.

METHODS

We collected blood samples from 203 Japanese patients with PD and analyzed various non-coding repeat genes, including , and , using PCR-Sanger sequencing, repeat-primed PCR assay, and long-read sequencing.

RESULTS

Three patients with PD (1.5%) were found to have heterozygous repeat expansions in the gene causative of spinocerebellar ataxia type 8 and is associated with long non-coding RNA. One (0.5%) patient had compound heterozygous repeat expansions (AAGGG and ACAGG) in , the gene causative of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, which encodes a DNA repair protein. No patient had repeat expansions in or . All patients with repeat expansions exhibited typical parkinsonism with relatively rare subjective dysphagia, which was confirmed by videofluoroscopic results. Functional imaging, such as dopamine-transporter single photon emission computed tomography, showed abnormal findings in patients with non-coding repeat expansions.

DISCUSSION

Our findings revealed the importance of non-coding repeat expansions in Japanese patients with PD. This is the first study to show the positive result of non-coding repeat expansions in many patients with PD in Japan.