Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis
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
Front. Med. ›› 2024, Vol. 18 ›› Issue (1) : 68 -80.
Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis
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.
TRMT2B / amyotrophic lateral sclerosis / mitochondrial complex I / tRNA methylation / reactive oxygen species
Higher Education Press
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