Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis

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 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

作者机构：Department of NeurologyXiangya HospitalCentral South UniversityJiangxiNational Regional Center for Neurological DiseasesNanchang330038China Provincial Laboratory for Diagnosis and Treatment of Genitourinary System DiseaseDepartment of UrologyXiangya HospitalCentral South UniversityChangsha410078China Department of OrthopedicsThe First Affiliated HospitalZhejiang University School of MedicineHangzhou310002China Department of NeurologyXiangya HospitalCentral South UniversityChangsha410078China National Clinical Research Center for Geriatric DiseasesXiangya HospitalCentral South UniversityChangsha410008China Key Laboratory of Hunan Province in Neurodegenerative DisordersCentral South UniversityChangsha410008China Center for Medical GeneticsSchool of Life SciencesCentral South UniversityChangsha410008China Engineering Research Center of Hunan Province in Cognitive Impairment DisordersCentral South UniversityChangsha410078China Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic DiseasesChangsha410078China Hunan Key Laboratory of Molecular Precision MedicineXiangya HospitalCentral South UniversityChangsha410078China 

出 版 物：《Frontiers of Medicine》 (医学前沿（英文版）)

年 卷 期：2024年第18卷第1期

页      面：68-80页

核心收录：

学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the Program of the National Natural Science Foundation of China(Nos.82171431 and 31972886) the Natural Science Fund for Distinguished Young Scholars of Hunan Province,China(Nos.2020JJ2057 and 2021JJ10074) Natural Science Foundation of Changsha City(No.kq2208402) the Program of the National Natural Science Foundation of Hunan Province(No.2021JJ40989) the Project Program of National Clinical Research Center for Geriatric Disorders at Xiangya Hospital(No.2020LNJJ13) the Science and Technology Innovation 2030(STI2030-Major Projects,No.2021ZD0201803) the National Key R&D Program of China(No.2021YFA0805202) the Innovation Team Project of Hunan Province(No.2019RS1010) the Innovation Team Project of Central South University(No.2020CX016) 

主　　题：TRMT2B amyotrophic lateral sclerosis mitochondrial complex I tRNA methylation reactive oxygen species 

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.1356GT;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 ***,TRMT2B variations overexpression cells also displayed decreased *** conclusion,a novel JALS-associated gene called TRMT2B was identified,thus broadening the clinical and genetic spectrum of ALS.