Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease

doi:10.1093/hmg/ddab257

	Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease
	Zheng, Wen-Qiang1,2 ; Pedersen, Signe Vandal 3; Thompson, Kyle 4; Bellacchio, Emanuele 5; French, Courtney E.6; Munro, Benjamin 7; Pearson, Toni S.8; Vogt, Julie 9; Diodato, Daria 10; Diemer, Tue 11; Ernst, Anja 12; Horvath, Rita 7; Chitre, Manali 13; Ek, Jakob 3; Wibrand, Flemming 3; Grange, Dorothy K.14; Raymond, Lucy 6; Zhou, Xiao-Long 1; Taylor, Robert W.4; Ostergaard, Elsebet 3,15
	2021-09-11
发表期刊	HUMAN MOLECULAR GENETICS
ISSN	0964-6906
EISSN	1460-2083
卷号	31 期号:4
发表状态	已发表
DOI	10.1093/hmg/ddab257
摘要	TARS2 encodes human mitochondrial threonyl tRNA-synthetase that is responsible for generating mitochondrial Thr-tRNAThr and clearing mischarged Ser-tRNAThr during mitochondrial translation. Pathogenic variants in TARS2 have hitherto been reported in a pair of siblings and an unrelated patient with an early onset mitochondrial encephalomyopathy and a combined respiratory chain enzyme deficiency in muscle. We here report five additional unrelated patients with TARS2-related mitochondrial diseases, expanding the clinical phenotype to also include epilepsy, dystonia, hyperhidrosis and severe hearing impairment. Additionally, we document seven novel TARS2 variants-one nonsense variant and six missense variants-that we demonstrate are pathogenic and causal of the disease presentation based on population frequency, homology modelling and functional studies that show the effects of the pathogenic variants on TARS2 stability and/or function.
学科门类	理学
URL	查看原文
收录类别	SCI ; SCIE
语种	英语
资助项目	Natural Science Foundation of China[31670801,31822015,81870896] ; Wellcome Centre for Mitochondrial Research[203105/Z/16/Z] ; Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular Disease[MR/S005021/1] ; Mitochondrial Disease Patient Cohort (UK)[G0800674] ; European Research Council[309548] ; Wellcome Investigator Award[109915/Z/15/Z] ; Medical Research Council (UK)[MR/N025431/1] ; Wellcome Trust Pathfinder Scheme[201064/Z/16/Z] ; Newton Fund (UK/Turkey)[MR/N027302/1]
WOS研究方向	Biochemistry & Molecular Biology ; Genetics & Heredity
WOS类目	Biochemistry & Molecular Biology ; Genetics & Heredity
WOS记录号	WOS:000776693700004
出版者	OXFORD UNIV PRESS
原始文献类型	wenqiang zheng
引用统计	被引频次：14[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/128196
专题	生命科学与技术学院_博士生
通讯作者	Zhou, Xiao-Long; Ostergaard, Elsebet
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab M, Shanghai 200031, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 3.Copenhagen Univ Hosp, Dept Clin Genet, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark 4.Newcastle Univ, Wellcome Ctr Mitochondrial Res, Translat & Clin Res Inst, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England 5.IRCCS, Bambino Gesu Childrens Hosp, Area Ric Genet & Malattie Rare, I-00165 Rome, Italy 6.Univ Cambridge, Dept Med Genet, Cambridge CB2 0QQ, England 7.Univ Cambridge, John Van Geest Ctr Brain Repair, Sch Clin Med, Dept Clin Neurosci, Cambridge CB2 0QQ, England 8.Washington Univ, Dept Neurol, Sch Med, St Louis, MO 63110 USA 9.Birmingham Womens & Childrens NHS Fdn Trust, Birmingham Womens Hosp, West Midlands Reg Genet Serv, Birmingham B15 2TG, W Midlands, England 10.Children Hosp Bambino Gesu, Neuromuscular & Neurodegenerat Dis Unit, I-00165 Rome, Italy 11.Aalborg Univ Hosp, Dept Clin Genet, DK-9000 Aalborg, Denmark 12.Aalborg Univ Hosp, Dept Mol Diagnost, DK-9000 Aalborg, Denmark 13.Cambridge Univ Hosp NHS Fdn Trust, Dept Paediat Neurol, Cambridge CB2 0QQ, England 14.Washington Univ, Dept Pediat, Div Genet & Genom Med, Sch Med, St Louis, MO 63110 USA 15.Univ Copenhagen, Dept Clin Med, DK-2200 Copenhagen, Denmark
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zheng, Wen-Qiang,Pedersen, Signe Vandal,Thompson, Kyle,et al. Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease[J]. HUMAN MOLECULAR GENETICS,2021,31(4).
APA	Zheng, Wen-Qiang.,Pedersen, Signe Vandal.,Thompson, Kyle.,Bellacchio, Emanuele.,French, Courtney E..,...&Ostergaard, Elsebet.(2021).Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease.HUMAN MOLECULAR GENETICS,31(4).
MLA	Zheng, Wen-Qiang,et al."Elucidating the molecular mechanisms associated with TARS2-related mitochondrial disease".HUMAN MOLECULAR GENETICS 31.4(2021).