Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder

doi:10.1007/s00109-024-02454-4

科研成果详情

题名	Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder
作者	Yuan, Xiangshu1; Wang, Ya1; Li, Xiyuan 2; Zhong, Sheng1; Zhou, Danyi1; Lin, Xianlong1; Fang, Hezhi1; Yang, Yanling 3; Wang, Maofeng4
发表日期	2024-05-16
发表期刊	Journal of molecular medicine (Berlin, Germany) 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	DDX53 HSP-like disorder Loss-of-function mutation RNA metabolism
其他关键词	BOX RNA HELICASE ; PROTEOLIPID PROTEIN GENE ; X-LINKED HYDROCEPHALUS ; OLIGODENDROCYTES ; MYELINATION ; TRAFFICKING ; SPECTRUM ; FEATURES ; STRESS
摘要	DEAD-box helicase 53 (DDX53) is a member of the DEAD-box protein family of RNA helicases. Unlike other family members that are responsible for RNA metabolism, the biological function of DDX53 and its impact on the human condition are unclear. Herein, we found a full-length DDX53 deletion mutation in a hereditary spastic paraplegia-like (HSP-like) patient with lower extremity spasticity, walking disorder, visual impairment, and lateral ventricular white matter lesions. Bioinformatic analysis revealed that DDX53 was mainly expressed in the cerebellar cortex and may function as a tissue-specific RNA helicase. Transcriptome analysis showed that the expression of multiple brain-associated genes involved in synapse organization, neuron function, and neuromuscular junctions was affected by DDX53 depletion. Moreover, RNA immunoprecipitation sequencing (RIP-seq) analysis showed that DDX53 interacted with 176 genes, and 96 of these genes were associated with the execution of neurofunction, particularly in the regulation of cell projection organization and nervous system development. Collectively, although a more specified cell or animal model is required to fully understand the functional role of DDX53 in the human brain, we report for the first time that the patient with DDX53 defects exhibits HSP-like symptoms and that DDX53 is essential for maintaining neuronal function, with loss-of-function mutation in DDX53 potentially leading to HSP due to impaired RNA metabolism in the nervous system. KEY MESSAGES: DDX53 deficiency was first reported to be associated with HSP disorder. DDX53 exhibited minimal impact on mitochondrial function. DDX53 impaired RNA metabolism in the nervous system.
资助项目	National Natural Science Foundation of China-excellent young scientists fund[82222043];the Pioneer and Leading Goose Research and Development Program of Zhejiang Province[2024C03152];Natural Science Foundation of China[82172322];the Natural Science Foundation of China[82302636];Zhejiang Provincial Natural Science Foundation[Q23H200001];Scientific Research Fund of Zhejiang Provincial Education Department[Y202249698];the Science and Technology Bureau of Wenzhou[Y2023089]
出版者	SPRINGER HEIDELBERG
ISSN	0946-2716
EISSN	1432-1440
卷号	102 期号:7 页码:913-926
DOI	10.1007/s00109-024-02454-4
页数	14
WOS类目	Genetics & Heredity ; Medicine, Research & Experimental
WOS研究方向	Genetics & Heredity ; Research & Experimental Medicine
WOS记录号	WOS:001226607900001
收录类别	PUBMED ; SCOPUS ; SCIE
URL	查看原文
PubMed ID	38753040
SCOPUSEID	2-s2.0-85193269149
通讯作者地址	[Fang, Hezhi]Key Laboratory of Laboratory Medicine,Ministry of Education,Zhejiang Provincial Key Laboratory of Medical Genetics,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China ; [Yang, Yanling]Department of Pediatrics,Peking University First Hospital,Beijing,100034,China ; [Wang, Maofeng]Department of Biomedical Sciences Laboratory,Affiliated Dongyang Hospital of Wenzhou Medical University,Zhejiang,Dongyang,322100,China
Scopus学科分类	Molecular Medicine;Drug Discovery;Genetics (clinical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212894
专题	检验医学院（生命科学学院、生物学实验教学中心）其他_附属东阳医院（东阳市人民医院）
通讯作者	Fang, Hezhi; Yang, Yanling; Wang, Maofeng
作者单位	1.Key Laboratory of Laboratory Medicine,Ministry of Education,Zhejiang Provincial Key Laboratory of Medical Genetics,School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Baylor Genetics,Houston,77030,United States; 3.Department of Pediatrics,Peking University First Hospital,Beijing,100034,China; 4.Department of Biomedical Sciences Laboratory,Affiliated Dongyang Hospital of Wenzhou Medical University,Zhejiang,Dongyang,322100,China
第一作者单位	检验医学院（生命科学学院、生物学实验教学中心）
通讯作者单位	检验医学院（生命科学学院、生物学实验教学中心）; 附属东阳医院（东阳市人民医院）
第一作者的第一单位	检验医学院（生命科学学院、生物学实验教学中心）
推荐引用方式 GB/T 7714	Yuan, Xiangshu,Wang, Ya,Li, Xiyuan,et al. Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder[J]. Journal of molecular medicine (Berlin, Germany),2024,102(7):913-926.
APA	Yuan, Xiangshu., Wang, Ya., Li, Xiyuan., Zhong, Sheng., Zhou, Danyi., ... & Wang, Maofeng. (2024). Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder. Journal of molecular medicine (Berlin, Germany), 102(7), 913-926.
MLA	Yuan, Xiangshu,et al."Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder".Journal of molecular medicine (Berlin, Germany) 102.7(2024):913-926.