Non-coding repeat analyses in patients with Parkinson’s disease
IntroductionThe 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 pathol...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-07-01
|
| Series: | Frontiers in Neurology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1606305/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849717500301803520 |
|---|---|
| author | Makito Hirano Makoto Samukawa Satoko Miyatake Satoko Miyatake Yuko Yamagishi Chiharu Isono Rino Yoshikawa Kazumasa Saigoh Atsushi Terayama Yuji Higashimoto Eriko Koshimizu Takeshi Mizuguchi Kanako Fujii Yoshiyuki Mitsui Naomichi Matsumoto Naomichi Matsumoto Naomichi Matsumoto Yoshitaka Nagai |
| author_facet | Makito Hirano Makoto Samukawa Satoko Miyatake Satoko Miyatake Yuko Yamagishi Chiharu Isono Rino Yoshikawa Kazumasa Saigoh Atsushi Terayama Yuji Higashimoto Eriko Koshimizu Takeshi Mizuguchi Kanako Fujii Yoshiyuki Mitsui Naomichi Matsumoto Naomichi Matsumoto Naomichi Matsumoto Yoshitaka Nagai |
| author_sort | Makito Hirano |
| collection | DOAJ |
| description | IntroductionThe 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.MethodsWe 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, using PCR-Sanger sequencing, repeat-primed PCR assay, and long-read sequencing.ResultsThree patients with PD (1.5%) were found to have heterozygous repeat expansions in ATXN8OS, 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 RFC1, the gene causative of 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 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.DiscussionOur 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. |
| format | Article |
| id | doaj-art-855c15f2a00c4f1bbfeb483374f8f29d |
| institution | DOAJ |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj-art-855c15f2a00c4f1bbfeb483374f8f29d2025-08-20T03:12:38ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-07-011610.3389/fneur.2025.16063051606305Non-coding repeat analyses in patients with Parkinson’s diseaseMakito Hirano0Makoto Samukawa1Satoko Miyatake2Satoko Miyatake3Yuko Yamagishi4Chiharu Isono5Rino Yoshikawa6Kazumasa Saigoh7Atsushi Terayama8Yuji Higashimoto9Eriko Koshimizu10Takeshi Mizuguchi11Kanako Fujii12Yoshiyuki Mitsui13Naomichi Matsumoto14Naomichi Matsumoto15Naomichi Matsumoto16Yoshitaka Nagai17Department of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Clinical Genetics, Yokohama City University Hospital, Yokohama, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDivision of Rehabilitation Medicine, Kindai University Hospital, Osakasayama, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Rehabilitation Medicine, Kindai University Faculty of Medicine, Osakasayama, JapanDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanDepartment of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, JapanDepartment of Clinical Genetics, Yokohama City University Hospital, Yokohama, JapanDepartment of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, JapanDepartment of Neurology, Kindai University Faculty of Medicine, Osaka, JapanIntroductionThe 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.MethodsWe 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, using PCR-Sanger sequencing, repeat-primed PCR assay, and long-read sequencing.ResultsThree patients with PD (1.5%) were found to have heterozygous repeat expansions in ATXN8OS, 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 RFC1, the gene causative of 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 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.DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1606305/fullspinocerebellar ataxia type 8repeat diseaseparkinsonismCanvasRFC1dysphagia |
| spellingShingle | Makito Hirano Makoto Samukawa Satoko Miyatake Satoko Miyatake Yuko Yamagishi Chiharu Isono Rino Yoshikawa Kazumasa Saigoh Atsushi Terayama Yuji Higashimoto Eriko Koshimizu Takeshi Mizuguchi Kanako Fujii Yoshiyuki Mitsui Naomichi Matsumoto Naomichi Matsumoto Naomichi Matsumoto Yoshitaka Nagai Non-coding repeat analyses in patients with Parkinson’s disease Frontiers in Neurology spinocerebellar ataxia type 8 repeat disease parkinsonism Canvas RFC1 dysphagia |
| title | Non-coding repeat analyses in patients with Parkinson’s disease |
| title_full | Non-coding repeat analyses in patients with Parkinson’s disease |
| title_fullStr | Non-coding repeat analyses in patients with Parkinson’s disease |
| title_full_unstemmed | Non-coding repeat analyses in patients with Parkinson’s disease |
| title_short | Non-coding repeat analyses in patients with Parkinson’s disease |
| title_sort | non coding repeat analyses in patients with parkinson s disease |
| topic | spinocerebellar ataxia type 8 repeat disease parkinsonism Canvas RFC1 dysphagia |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1606305/full |
| work_keys_str_mv | AT makitohirano noncodingrepeatanalysesinpatientswithparkinsonsdisease AT makotosamukawa noncodingrepeatanalysesinpatientswithparkinsonsdisease AT satokomiyatake noncodingrepeatanalysesinpatientswithparkinsonsdisease AT satokomiyatake noncodingrepeatanalysesinpatientswithparkinsonsdisease AT yukoyamagishi noncodingrepeatanalysesinpatientswithparkinsonsdisease AT chiharuisono noncodingrepeatanalysesinpatientswithparkinsonsdisease AT rinoyoshikawa noncodingrepeatanalysesinpatientswithparkinsonsdisease AT kazumasasaigoh noncodingrepeatanalysesinpatientswithparkinsonsdisease AT atsushiterayama noncodingrepeatanalysesinpatientswithparkinsonsdisease AT yujihigashimoto noncodingrepeatanalysesinpatientswithparkinsonsdisease AT erikokoshimizu noncodingrepeatanalysesinpatientswithparkinsonsdisease AT takeshimizuguchi noncodingrepeatanalysesinpatientswithparkinsonsdisease AT kanakofujii noncodingrepeatanalysesinpatientswithparkinsonsdisease AT yoshiyukimitsui noncodingrepeatanalysesinpatientswithparkinsonsdisease AT naomichimatsumoto noncodingrepeatanalysesinpatientswithparkinsonsdisease AT naomichimatsumoto noncodingrepeatanalysesinpatientswithparkinsonsdisease AT naomichimatsumoto noncodingrepeatanalysesinpatientswithparkinsonsdisease AT yoshitakanagai noncodingrepeatanalysesinpatientswithparkinsonsdisease |