Li-Ting Jiang1, Li-Xi Li2, Ying Liu3, Xiao-Long Zhang4, You-Gui Pan5, Lin Wang6, Xin-Hua Wan7, Ling-Jing Jin8. 1. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: litinjiang@126.com. 2. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: lixili@tongji.edu.cn. 3. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: Liuyingneurology@163.com. 4. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: kqljzxl@126.com. 5. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: 75620465@qq.com. 6. Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. Electronic address: 13910699693@139.com. 7. Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China. Electronic address: xhwanpumch@hotmail.com. 8. Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: lingjingjin@163.com.
Abstract
INTRODUCTION: Dystonia is a movement disorder with high clinical and genetic heterogeneity. Mutations in Anoctamin-3 (ANO3) gene have been reported to cause dystonia 24 (DYT24). This study aims to clarify the spectrum and frequency of ANO3 rare variants in Chinese populations with primary dystonia and understand the clinical and genetic features of DYT24. METHODS: Sanger sequencing was used to screen all exons and exon-intron boundaries of ANO3 for rare variants in 115 primary dystonia patients. The clinical manifestations of patients with ANO3 variants in our study and previously reported literatures were further characterized. RESULTS: Four distinct variants of ANO3 (c.1127A > G, c.1235 T > A, c.1531-3T > C, c.-11G > T) were identified in six unrelated individuals. Combined with our work and literature review, a total of 35 different rare variants distributed in ANO3 were identified in 62 dystonia patients. The predominant phenotype is cranio-cervical dystonia and more than half of patients develop head/limb tremor. Most of patients presented with isolated dystonia whereas few of them showed combined dystonia. The age of onset ranged from 1 to 69 years and peaked in late adulthood, while for generalized dystonia it peaked in a young age. Half of patients with generalized dystonia experienced deep brain stimulation (DBS). And all of them showed improvement of dystonia by DBS. CONCLUSIONS: This study confirms a relatively high frequency of rare ANO3 variants in Chinese patients with dystonia and indicates that the late adulthood-onset, cranio-cervical dystonia seems to be an important feature of the ANO3 phenotype. Further functional studies are warranted to understand the role of ANO3 in dystonia.
INTRODUCTION:Dystonia is a movement disorder with high clinical and genetic heterogeneity. Mutations in Anoctamin-3 (ANO3) gene have been reported to cause dystonia 24 (DYT24). This study aims to clarify the spectrum and frequency of ANO3 rare variants in Chinese populations with primary dystonia and understand the clinical and genetic features of DYT24. METHODS: Sanger sequencing was used to screen all exons and exon-intron boundaries of ANO3 for rare variants in 115 primary dystoniapatients. The clinical manifestations of patients with ANO3 variants in our study and previously reported literatures were further characterized. RESULTS: Four distinct variants of ANO3 (c.1127A > G, c.1235 T > A, c.1531-3T > C, c.-11G > T) were identified in six unrelated individuals. Combined with our work and literature review, a total of 35 different rare variants distributed in ANO3 were identified in 62 dystoniapatients. The predominant phenotype is cranio-cervical dystonia and more than half of patients develop head/limb tremor. Most of patients presented with isolated dystonia whereas few of them showed combined dystonia. The age of onset ranged from 1 to 69 years and peaked in late adulthood, while for generalized dystonia it peaked in a young age. Half of patients with generalized dystonia experienced deep brain stimulation (DBS). And all of them showed improvement of dystonia by DBS. CONCLUSIONS: This study confirms a relatively high frequency of rare ANO3 variants in Chinese patients with dystonia and indicates that the late adulthood-onset, cranio-cervical dystonia seems to be an important feature of the ANO3 phenotype. Further functional studies are warranted to understand the role of ANO3 in dystonia.
Authors: Lazzaro di Biase; Alessandro Di Santo; Maria Letizia Caminiti; Pasquale Maria Pecoraro; Simona Paola Carbone; Vincenzo Di Lazzaro Journal: J Clin Med Date: 2022-07-19 Impact factor: 4.964