ORIGINAL RESEARCH article

Front. Neurol.

Sec. Movement Disorders

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1606305

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

Provisionally accepted
Makito HiranoMakito Hirano1*Makoto SamukawaMakoto Samukawa1Satoko MiyatakeSatoko Miyatake2,3Yuko YamagishiYuko Yamagishi1Chiharu IsonoChiharu Isono4Rino YoshikawaRino Yoshikawa1Kazumasa SaigohKazumasa Saigoh1Atsushi TerayamaAtsushi Terayama1Yuji HigasimotoYuji Higasimoto5Eriko KoshimizuEriko Koshimizu2Takeshi MizuguchiTakeshi Mizuguchi2Kanako FujiiKanako Fujii1Yoshiyuki MitsuiYoshiyuki Mitsui1Naomichi MatsumotoNaomichi Matsumoto2,3,6Yoshitaka NagaiYoshitaka Nagai1
  • 1Department of Neurology, Faculty of Medicine, Kindai University, Osaka, Japan
  • 2Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
  • 3Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan
  • 4Division of Rehabilitation Medicine, Kindai University Hospital, Japan, Osakasayama, Japan
  • 5Department of Rehabilitation Medicine, Faculty of Medicine, Kindai University, Osakasayama, Japan
  • 6Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Kanagawa, Japan

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The genetic etiology for Parkinson's disease (PD) is complexed; about 10% of patients with PD are associated with various gene mutations causative for familial PD. Recent analyses of non-coding repeat regions revealed that many neurodegenerative diseases are associated with pathological expansions. We evaluated the genetic background for non-coding repeat expansions in Japanese patients with PD.We collected blood samples from 203 Japanese patients with PD and analyzed various non-coding repeat genes, including ATXN8OS, RFC1, C9ORF72, NOTCH2NLC, BEAN1/TK2, and NOP56 by PCR-Sanger sequencing, repeat-primed PCR assay, and long-read sequencing.Results: Three patients with PD (1.5%) had heterozygous repeat expansions in ATXN8OS, the gene causative for spinocerebellar ataxia type 8 and associated with long non-coding RNA. One (0.5%) had compound heterozygous repeat expansions (AAGGG and ACAGG) in RFC1, the gene causative for cerebellar ataxia, neuropathy, and vestibular areflexia syndrome, which encodes a DNA repair protein. No patient had repeat expansions in C9ORF72, NOTCH2NLC, BEAN1/TK2, or NOP56. All the Hirano, M. et al. Page 7 patients with ATXN8OS 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 finding reveals the importance of non-coding repeat expansions in Japanese patients with PD. This is the first study to show the positive result of noncoding repeat expansions in a large number of patients with PD in Japan.

Keywords: Spinocerebellar ataxia type 8, Repeat disease, parkinsonism, Canvas, RFC1, dysphagia, videofluoroscopic analysis

Received: 05 Apr 2025; Accepted: 16 Jun 2025.

Copyright: © 2025 Hirano, Samukawa, Miyatake, Yamagishi, Isono, Yoshikawa, Saigoh, Terayama, Higasimoto, Koshimizu, Mizuguchi, Fujii, Mitsui, Matsumoto and Nagai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Makito Hirano, Department of Neurology, Faculty of Medicine, Kindai University, Osaka, 589-8511, Japan

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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