The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China
Abstract So far, over 20 causative genes of monogenic Parkinson’s disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early o...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-05-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-023-00518-9 |
| _version_ | 1797422470370689024 |
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| author | Yi-Min Sun Xin-Yue Zhou Xiao-Niu Liang Jin-Ran Lin Yi-Dan Xu Chen Chen Si-Di Wei Qi-Si Chen Feng-Tao Liu Jue Zhao Yi-Lin Tang Bo Shen Lin-Hua Gan Boxun Lu Zheng-Tong Ding Yu An Jian-Jun Wu Jian Wang |
| author_facet | Yi-Min Sun Xin-Yue Zhou Xiao-Niu Liang Jin-Ran Lin Yi-Dan Xu Chen Chen Si-Di Wei Qi-Si Chen Feng-Tao Liu Jue Zhao Yi-Lin Tang Bo Shen Lin-Hua Gan Boxun Lu Zheng-Tong Ding Yu An Jian-Jun Wu Jian Wang |
| author_sort | Yi-Min Sun |
| collection | DOAJ |
| description | Abstract So far, over 20 causative genes of monogenic Parkinson’s disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders. |
| first_indexed | 2024-03-09T07:32:45Z |
| format | Article |
| id | doaj.art-e271155b6d364fe2ace5dd21d8814500 |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-09T07:32:45Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-e271155b6d364fe2ace5dd21d88145002023-12-03T06:06:44ZengNature Portfolionpj Parkinson's Disease2373-80572023-05-01911910.1038/s41531-023-00518-9The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland ChinaYi-Min Sun0Xin-Yue Zhou1Xiao-Niu Liang2Jin-Ran Lin3Yi-Dan Xu4Chen Chen5Si-Di Wei6Qi-Si Chen7Feng-Tao Liu8Jue Zhao9Yi-Lin Tang10Bo Shen11Lin-Hua Gan12Boxun Lu13Zheng-Tong Ding14Yu An15Jian-Jun Wu16Jian Wang17Department of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityHuman Phenome Institute, Zhangjiang Fudan International Innovation Center, MOE Key Laboratory of Contemporary Anthropology, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, School of Life Sciences, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityHuman Phenome Institute, Zhangjiang Fudan International Innovation Center, MOE Key Laboratory of Contemporary Anthropology, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityDepartment of Neurology and National Research Center for Aging and Medicine & National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Huashan Hospital, Fudan UniversityAbstract So far, over 20 causative genes of monogenic Parkinson’s disease (PD) have been identified. Some causative genes of non-parkinsonian entities may also manifest with parkinsonism mimicking PD. This study aimed to investigate the genetic characteristics of clinically diagnosed PD with early onset age or family history. A total of 832 patients initially diagnosed with PD were enrolled, of which, 636 were classified into the early-onset group and 196 were classified into the familial late-onset group. The genetic testing included the multiplex ligation-dependent probe amplification and next generation sequencing (target sequencing or whole-exome sequencing). The dynamic variants of spinocerebellar ataxia were tested in probands with family history. In the early-onset group, 30.03% of patients (191/636) harbored pathogenic/likely pathogenic (P/LP) variants in known PD-related genes (CHCHD2, DJ-1, GBA (heterozygous), LRRK2, PINK1, PRKN, PLA2G6, SNCA and VPS35). Variants in PRKN were the most prevalent, accounting for 15.72% of the early-onset patients, followed by GBA (10.22%), and PLA2G6 (1.89%). And 2.52% (16/636) had P/LP variants in causative genes of other diseases (ATXN3, ATXN2, GCH1, TH, MAPT, GBA (homozygous)). In the familial late-onset group, 8.67% of patients (17/196) carried P/LP variants in known PD-related genes (GBA (heterozygous), HTRA2, SNCA) and 2.04% (4/196) had P/LP variants in other genes (ATXN2, PSEN1, DCTN1). Heterozygous GBA variants (7.14%) were the most common genetic cause found in familial late-onset patients. Genetic testing is of vital importance in differential diagnosis especially in early-onset and familial PD. Our findings may also provide some clues to the nomenclature of genetic movement disorders.https://doi.org/10.1038/s41531-023-00518-9 |
| spellingShingle | Yi-Min Sun Xin-Yue Zhou Xiao-Niu Liang Jin-Ran Lin Yi-Dan Xu Chen Chen Si-Di Wei Qi-Si Chen Feng-Tao Liu Jue Zhao Yi-Lin Tang Bo Shen Lin-Hua Gan Boxun Lu Zheng-Tong Ding Yu An Jian-Jun Wu Jian Wang The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China npj Parkinson's Disease |
| title | The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China |
| title_full | The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China |
| title_fullStr | The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China |
| title_full_unstemmed | The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China |
| title_short | The genetic spectrum of a cohort of patients clinically diagnosed as Parkinson’s disease in mainland China |
| title_sort | genetic spectrum of a cohort of patients clinically diagnosed as parkinson s disease in mainland china |
| url | https://doi.org/10.1038/s41531-023-00518-9 |
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