Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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外文摘要：Amyotrophic lateral sclerosis(ALS)is a fatal neurodegenerative disease characterized by progressive degeneration of motor neurons,and it demonstrates high clinical heterogeneity and complex genetic architecture.A variation within TRMT2B(c.1356G＞T;p.K452N)was identified to be associated with ALS in a family comprising two patients with juvenile ALS(JALS).Two missense variations and one splicing variation were identified in 10 patients with ALS in a cohort with 910 patients with ALS,and three more variants were identified in a public ALS database including 3317 patients with ALS.A decreased number of mitochondria,swollen mitochondria,lower expression of ND1,decreased mitochondrial complex I activities,lower mitochondrial aerobic respiration,and a high level of ROS were observed functionally in patient-originated lymphoblastoid cell lines and TRMT2B interfering HEK293 cells.Further,TRMT2B variations overexpression cells also displayed decreased ND1.In conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.

外文关键词：

TRMT2Bamyotrophic lateral sclerosismitochondrial complex ItRNA methylationreactive oxygen species

作者：

Yanling Liu、Xi He、Yanchun Yuan、Bin Li、Zhen Liu、Wanzhen Li、Kaixuan Li、Shuo Tan、Quan Zhu、Zhengyan Tang、Feng Han、Ziqiang Wu、Lu Shen、Hong Jiang、Beisha Tang、Jian Qiu、Zhengmao Hu、Junling Wang

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作者单位：

Department of Neurology,Xiangya Hospital,Central South University,Jiangxi,National Regional Center for Neurological Diseases,Nanchang 330038 China

Provincial Laboratory for Diagnosis and Treatment of Genitourinary System Disease,Department of Urology,Xiangya Hospital,Central South University,Changsha 410078,China

Department of Orthopedics,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310002,China

Department of Neurology,Xiangya Hospital,Central South University,Changsha 410078,China

National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Central South University,Changsha 410008,China

Key Laboratory of Hunan Province in Neurodegenerative Disorders,Central South University,Changsha 410008,China

Center for Medical Genetics,School of Life Sciences,Central South University,Changsha 410008,China

Engineering Research Center of Hunan Province in Cognitive Impairment Disorders,Central South

Hunan Key Laboratory of Molecular Precision Medicine,Xiangya Hospital,Central South University,Changsha 410078,China

Center for Medical Genetics,School of Life Sc

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基金：

国家自然科学基金国家自然科学基金Natural Science Fund for Distinguished Young Scholars of Hunan Province,ChinaNatural Science Fund for Distinguished Young Scholars of Hunan Province,China长沙市自然科学基金Program of the National Natural Science Foundation of Hunan ProvinceProject Program of National Clinical Research Center for Geriatric Disorders at Xiangya HospitalScience and Technology Innovation 2030Science and Technology Innovation 2030国家重点研发计划Innovation Team Project of Hunan ProvinceInnovation Team Project of Central South University

项目编号：

82171431319728862020JJ20572021JJ10074kq22084022021JJ409892020LNJJ13STI2030-Major Projects2021ZD02018032021YFA08052022019RS10102020CX016

出版年：

2024

DOI：

10.1007/s11684-023-1005-y

医学前沿

高等教育出版社

医学前沿

CSTPCD

影响因子：1.362

ISSN：2095-0217

年,卷(期)：2024.18(1)

参考文献量41