Association of TRMT2B gene variants with juvenile amyotrophic lateral sclerosis.
Front Med
; 18(1): 68-80, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-37874476
ABSTRACT
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.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
Front Med
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China