Human Mutation, volume 41, issue 5, pages 961-972
Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency
Wei Xiujuan
1
,
Du Miaomiao
1
,
Li Dongxiao
2
,
Wen Shumeng
1, 3
,
Xie Jie
1
,
Li Yuanyuan
1
,
Chen Aolong
1
,
Zhang Kun
1
,
Xu Pu
1
,
Jia Manli
1
,
Wen Chaowei
1
,
Zhou Huaibin
1
,
Lyu Jianxin
1, 4
,
Yang Yanling
5
,
Fang Hezhi
1
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 sciencesWenzhou Medical UniversityWenzhou China
|
2
Department of Henan Provincial Key Laboratory of Children's Genetics and Metabolic DiseasesChildren's Hospital Affiliated to Zhengzhou UniversityZhengzhou China
|
3
Department of Clinical LaboratoryQingdao Municipal Hospital (Group)Qingdao China
|
4
Department of Laboratory Medicine, Zhejiang Provincial People's HospitalAffiliated People's Hospital of Hangzhou Medical CollegeHangzhou China
|
Publication type: Journal Article
Publication date: 2020-01-30
Journal:
Human Mutation
Quartile SCImago
Q1
Quartile WOS
Q2
Impact factor: 3.9
ISSN: 10597794, 10981004
Genetics
Genetics (clinical)
Abstract
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.
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Wei X. et al. Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency // Human Mutation. 2020. Vol. 41. No. 5. pp. 961-972.
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Wei X., Du M., Li D., Wen S., Xie J., Li Y., Chen A., Zhang K., Xu P., Jia M., Wen C., Zhou H., Lyu J., Yang Y., Fang H. Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency // Human Mutation. 2020. Vol. 41. No. 5. pp. 961-972.
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TY - JOUR
DO - 10.1002/humu.23985
UR - https://doi.org/10.1002%2Fhumu.23985
TI - Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency
T2 - Human Mutation
AU - Du, Miaomiao
AU - Li, Dongxiao
AU - Wen, Shumeng
AU - Xie, Jie
AU - Chen, Aolong
AU - Xu, Pu
AU - Jia, Manli
AU - Wen, Chaowei
AU - Zhou, Huaibin
AU - Fang, Hezhi
AU - Wei, Xiujuan
AU - Li, Yuanyuan
AU - Zhang, Kun
AU - Lyu, Jianxin
AU - Yang, Yanling
PY - 2020
DA - 2020/01/30 00:00:00
PB - Wiley
SP - 961-972
IS - 5
VL - 41
SN - 1059-7794
SN - 1098-1004
ER -
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@article{2020_Wei,
author = {Miaomiao Du and Dongxiao Li and Shumeng Wen and Jie Xie and Aolong Chen and Pu Xu and Manli Jia and Chaowei Wen and Huaibin Zhou and Hezhi Fang and Xiujuan Wei and Yuanyuan Li and Kun Zhang and Jianxin Lyu and Yanling Yang},
title = {Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency},
journal = {Human Mutation},
year = {2020},
volume = {41},
publisher = {Wiley},
month = {jan},
url = {https://doi.org/10.1002%2Fhumu.23985},
number = {5},
pages = {961--972},
doi = {10.1002/humu.23985}
}
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MLA
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Wei, Xiujuan, et al. “Mutations in FASTKD2 are associated with mitochondrial disease with multi‐OXPHOS deficiency.” Human Mutation, vol. 41, no. 5, Jan. 2020, pp. 961-972. https://doi.org/10.1002%2Fhumu.23985.