Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease
Background: Genetic and epigenetic modifiers of age at onset of Parkinson’s disease (PD) are largely unknown. It remains unclear whether DNA methylation (DNAm) age acceleration is linked to age at onset in PD patients of different ethnicities with a similar genetic background. We aim to characterize...
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MDPI AG
2023-04-01
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| Series: | Clinical and Translational Neuroscience |
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| Online Access: | https://www.mdpi.com/2514-183X/7/2/11 |
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| author | Yi-Min Sun Wan-Li Yang Ekaterina Rogaeva Anthony E. Lang Jian Wang Ming Zhang |
| author_facet | Yi-Min Sun Wan-Li Yang Ekaterina Rogaeva Anthony E. Lang Jian Wang Ming Zhang |
| author_sort | Yi-Min Sun |
| collection | DOAJ |
| description | Background: Genetic and epigenetic modifiers of age at onset of Parkinson’s disease (PD) are largely unknown. It remains unclear whether DNA methylation (DNAm) age acceleration is linked to age at onset in PD patients of different ethnicities with a similar genetic background. We aim to characterize the clinical, genomic and epigenomic features of three pairs of Chinese monozygotic twins discordant for PD onset by up to 10 years. Methods: We conducted whole genome sequencing, multiplex ligation-dependent probe amplification and genome-wide DNAm array to evaluate the three pairs of Chinese monozygotic twins discordant for age at onset of PD (families A–C). Results: We identified two heterozygous PRKN mutations (exon 2–4 deletion and p.Met1Thr) in PD affected members of one family. Somatic mutation analyses of investigated families did not reveal any variants that could explain the phenotypic discordance in the twin pairs. Of note, our epigenetic study revealed that the twins with earlier-onset had a trend of faster DNAm age acceleration than the later-onset/asymptomatic twins, but without statistical significance. Conclusion: The link between DNAm age acceleration and PD onset in Chinese patients should be interpreted with cautious, and need to be further verified in an extended PD cohort with similar genetic background. |
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| format | Article |
| id | doaj.art-fc52d68646e54f7484c54cf85b5b9667 |
| institution | Directory Open Access Journal |
| issn | 2514-183X |
| language | English |
| last_indexed | 2024-03-11T02:36:22Z |
| publishDate | 2023-04-01 |
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| spelling | doaj.art-fc52d68646e54f7484c54cf85b5b96672023-11-18T09:57:30ZengMDPI AGClinical and Translational Neuroscience2514-183X2023-04-01721110.3390/ctn7020011Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s DiseaseYi-Min Sun0Wan-Li Yang1Ekaterina Rogaeva2Anthony E. Lang3Jian Wang4Ming Zhang5Department of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Medical Genetics, The First Rehabilitation Hospital of Shanghai, School of Medicine, Tongji University, Shanghai 200090, ChinaTanz Centre for Research in Neurodegenerative Diseases, University of Toronto, 60 Leonard Ave., Toronto, ON M5T 2S8, CanadaDivision of Neurology, University of Toronto, Toronto, ON M5R 0A3, CanadaDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Medical Genetics, The First Rehabilitation Hospital of Shanghai, School of Medicine, Tongji University, Shanghai 200090, ChinaBackground: Genetic and epigenetic modifiers of age at onset of Parkinson’s disease (PD) are largely unknown. It remains unclear whether DNA methylation (DNAm) age acceleration is linked to age at onset in PD patients of different ethnicities with a similar genetic background. We aim to characterize the clinical, genomic and epigenomic features of three pairs of Chinese monozygotic twins discordant for PD onset by up to 10 years. Methods: We conducted whole genome sequencing, multiplex ligation-dependent probe amplification and genome-wide DNAm array to evaluate the three pairs of Chinese monozygotic twins discordant for age at onset of PD (families A–C). Results: We identified two heterozygous PRKN mutations (exon 2–4 deletion and p.Met1Thr) in PD affected members of one family. Somatic mutation analyses of investigated families did not reveal any variants that could explain the phenotypic discordance in the twin pairs. Of note, our epigenetic study revealed that the twins with earlier-onset had a trend of faster DNAm age acceleration than the later-onset/asymptomatic twins, but without statistical significance. Conclusion: The link between DNAm age acceleration and PD onset in Chinese patients should be interpreted with cautious, and need to be further verified in an extended PD cohort with similar genetic background.https://www.mdpi.com/2514-183X/7/2/11monozygotic twinsParkinson’s diseasegeneticsepigeneticsage at onset |
| spellingShingle | Yi-Min Sun Wan-Li Yang Ekaterina Rogaeva Anthony E. Lang Jian Wang Ming Zhang Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease Clinical and Translational Neuroscience monozygotic twins Parkinson’s disease genetics epigenetics age at onset |
| title | Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease |
| title_full | Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease |
| title_fullStr | Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease |
| title_full_unstemmed | Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease |
| title_short | Genetic and Epigenetic Study of Monozygotic Twins Affected by Parkinson’s Disease |
| title_sort | genetic and epigenetic study of monozygotic twins affected by parkinson s disease |
| topic | monozygotic twins Parkinson’s disease genetics epigenetics age at onset |
| url | https://www.mdpi.com/2514-183X/7/2/11 |
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