Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency

doi:10.1002/humu.23985

科研成果详情

题名	Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency
作者	Wei, Xiujuan1; Du, Miaomiao 1; Li, Dongxiao 2; Wen, Shumeng 1,3; Xie, Jie1; Li, Yuanyuan1; Chen, Aolong 1; Zhang, Kun1; Xu, Pu 1; Jia, Manli1; Wen, Chaowei1; Zhou, Huaibin1; Lyu, Jianxin 1,4; Yang, Yanling 5; Fang, Hezhi1
发表日期	2020-05
发表期刊	HUMAN MUTATION 影响因子和分区
语种	英语
原始文献类型	Article
关键词	FASTKD2 metabolic genetic diseases mitochondrial disease OXPHOS complex
其他关键词	RNA GRANULES ; PROTEIN
摘要	Mutations in FASTKD2, a mitochondrial RNA binding protein, have been associated with mitochondrial encephalomyopathy with isolated complex IV deficiency. However, deficiencies related to other oxidative phosphorylation system (OXPHOS) complexes have not been reported. Here, we identified three novel FASTKD2 mutations, c.808_809insTTTCAGTTTTG, homoplasmic mutation c.868C>T, and heteroplasmic mutation c.1859delT/c.868C>T, in patients with mitochondrial encephalomyopathy. Cell-based complementation assay revealed that these three FASTKD2 mutations were pathogenic. Mitochondrial functional analysis revealed that mutations in FASTKD2 impaired the mitochondrial function in patient-derived lymphocytes due to the deficiency in multi-OXPHOS complexes, whereas mitochondrial complex II remained unaffected. Consistent results were also found in human primary muscle cell and zebrafish with knockdown of FASTKD2. Furthermore, we discovered that FASTKD2 mutation is not inherently associated with epileptic seizures, optic atrophy, and loss of visual function. Alternatively, a patient with FASTKD2 mutation can show sinus tachycardia and hypertrophic cardiomyopathy, which was partially confirmed in zebrafish with knockdown of FASTKD2. In conclusion, both in vivo and in vitro studies suggest that loss of function mutation in FASTKD2 is responsible for multi-OXPHOS complexes deficiency, and FASTKD2-associated mitochondrial disease has a high degree of clinical heterogenicity.
资助项目	National Natural Science Foundation of China[81741061];
出版者	WILEY
出版地	HOBOKEN
ISSN	1059-7794
EISSN	1098-1004
卷号	41 期号:5 页码:961-972
DOI	10.1002/humu.23985
页数	12
WOS类目	Genetics & Heredity
WOS研究方向	Genetics & Heredity
WOS记录号	WOS:000525388300009
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31944455
SCOPUSEID	2-s2.0-85078863784
通讯作者地址	[Lyu, Jianxin]Key Laboratory of Laboratory Medicine,Ministry of Education,Zhejiang Provincial Key Laboratory of Medical Genetics,Department of Cell Biology and Medical Genetics,College of Laboratory Medicine and Life sciences,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Genetics;Genetics (clinical)
引用统计	被引频次：13[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/11514
专题	基础医学院（机能实验教学中心）_生物科学系_细胞生物学检验医学院（生命科学学院、生物学实验教学中心）
通讯作者	Lyu, Jianxin
作者单位	1.Key Laboratory of Laboratory Medicine,Ministry of Education,Zhejiang Provincial Key Laboratory of Medical Genetics,Department of Cell Biology and Medical Genetics,College of Laboratory Medicine and Life sciences,Wenzhou Medical University,Wenzhou,China; 2.Department of Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases,Children's Hospital Affiliated to Zhengzhou University,Zhengzhou,China; 3.Department of Clinical Laboratory,Qingdao Municipal Hospital (Group),Qingdao,China; 4.Department of Laboratory Medicine,Zhejiang Provincial People's Hospital,Affiliated People's Hospital of Hangzhou Medical College,Hangzhou,China; 5.Department of Pediatrics,Peking University First Hospital,Beijing,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）
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	Wei, Xiujuan,Du, Miaomiao,Li, Dongxiao,et al. Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency[J]. HUMAN MUTATION,2020,41(5):961-972.
APA	Wei, Xiujuan., Du, Miaomiao., Li, Dongxiao., Wen, Shumeng., Xie, Jie., ... & Fang, Hezhi. (2020). Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency. HUMAN MUTATION, 41(5), 961-972.
MLA	Wei, Xiujuan,et al."Mutations in FASTKD2 are associated with mitochondrial disease with multi-OXPHOS deficiency".HUMAN MUTATION 41.5(2020):961-972.