{"title":"Clinical and Genetic Findings in a Chinese Cohort of Dentatorubral-Pallidoluysian Atrophy Patients.","authors":"Ru-Ying Yuan, Ya-Fang Chen, Wei Lin, Meng-Cheng Li, Yi-Heng Zeng, Bi Cheng, Xin-Tong Yu, Dan-Dan Zuo, Hua-Mei Sun, Bei-Ning Ye, Ying-Xin Ye, Mao-Lin Cui, Nai-Qing Cai, Yu Lin, Qi-Jie Zhang, Yu-Sen Qiu, Lin-Wei Zhang, Xing-Wang Song, Jia-Na Wei, Li-Ying Pan, Ya-Yun Yan, Yi-Min Sun, Jin-Tai Yu, Zhi-Ying Wu, Yi Dong, Chun-Yan Cao, Chao Wu, Jie Zu, Yuan-Yuan Dai, Xian-Jin Shang, Hai-Tao Zhou, Min-Jin Wang, Qing Ke, En-Lin Dong, Yi-Feng Xiao, Zi-Yue Ouyang, Xin-Yuan Chen, Jian-Ping Hu, Min-Ting Lin, Ying Fu, Wan-Jin Chen, Ning Wang, Shi-Rui Gan","doi":"10.1002/ana.27293","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, inherited neurodegenerative disorder caused by the expansion of cytosine-adenine-guanine repeats in ATN1. Most studies on DRPLA to date are limited to case reports. We aimed to provide a comprehensive summary of the clinical, genetic, biological, and magnetic resonance imaging characteristics of DRPLA using cross-sectional baseline data.</p><p><strong>Methods: </strong>This is a cross-sectional observational cohort study. We used an extensive battery of assessments, included clinical phenotypes, genotypes, cognitive performance, biological markers, and magnetic resonance imaging characteristics.</p><p><strong>Results: </strong>We enrolled 116 DRPLA patients, including 96 manifest patients and 20 prodromal patients. We identified a previously unreported ATN1 haplotype consisting of 8 single-nucleotide polymorphisms. Cognitive assessments revealed that 51 manifest patients (96%) and 4 prodromal patients (29%) scored <26 on the Montreal Cognitive Assessment. Manifest patients showed impairments across all cognitive domains, whereas prodromal patients showed deficits only in phonemic fluency. Biological analyses showed significantly elevated plasma neurofilament light levels in manifest patients compared with prodromal patients (P < 0.001) and healthy controls (P < 0.001). Magnetic resonance imaging findings revealed widespread gray matter loss across the whole brain in manifest patients, whereas prodromal patients showed gray matter loss localized to the bilateral cerebellar hemispheres.</p><p><strong>Interpretation: </strong>This is the first DRPLA cohort study to comprehensively report clinical, genetic, cognitive, imaging, and plasma neurofilament light data. This study provides robust data to enhance our understanding of the overall features of DRPLA. We also propose clear definitions for the preclinical stage of DRPLA, and demonstrate the high diagnostic utility of plasma neurofilament light as a biomarker. ANN NEUROL 2025.</p>","PeriodicalId":127,"journal":{"name":"Annals of Neurology","volume":" ","pages":""},"PeriodicalIF":8.1000,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/ana.27293","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare, inherited neurodegenerative disorder caused by the expansion of cytosine-adenine-guanine repeats in ATN1. Most studies on DRPLA to date are limited to case reports. We aimed to provide a comprehensive summary of the clinical, genetic, biological, and magnetic resonance imaging characteristics of DRPLA using cross-sectional baseline data.
Methods: This is a cross-sectional observational cohort study. We used an extensive battery of assessments, included clinical phenotypes, genotypes, cognitive performance, biological markers, and magnetic resonance imaging characteristics.
Results: We enrolled 116 DRPLA patients, including 96 manifest patients and 20 prodromal patients. We identified a previously unreported ATN1 haplotype consisting of 8 single-nucleotide polymorphisms. Cognitive assessments revealed that 51 manifest patients (96%) and 4 prodromal patients (29%) scored <26 on the Montreal Cognitive Assessment. Manifest patients showed impairments across all cognitive domains, whereas prodromal patients showed deficits only in phonemic fluency. Biological analyses showed significantly elevated plasma neurofilament light levels in manifest patients compared with prodromal patients (P < 0.001) and healthy controls (P < 0.001). Magnetic resonance imaging findings revealed widespread gray matter loss across the whole brain in manifest patients, whereas prodromal patients showed gray matter loss localized to the bilateral cerebellar hemispheres.
Interpretation: This is the first DRPLA cohort study to comprehensively report clinical, genetic, cognitive, imaging, and plasma neurofilament light data. This study provides robust data to enhance our understanding of the overall features of DRPLA. We also propose clear definitions for the preclinical stage of DRPLA, and demonstrate the high diagnostic utility of plasma neurofilament light as a biomarker. ANN NEUROL 2025.
期刊介绍：
Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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