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PHACTR1 is associated with disease progression in Chinese Moyamoya disease

Moyamoya disease (MMD) is a progressive stenosis at the terminal portion of internal carotid artery and frequently occurs in East Asian countries. The etiology of MMD is still largely unknown. We performed a case-control design with whole-exome sequencing analysis on 31 sporadic MMD patients and 10...

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Autores principales: Yang, Yongbo, Wang, Jian, Liang, Qun, Wang, Yi, Chen, Xinhua, Zhang, Qingrong, Na, Shijie, Liu, Yi, Yan, Ting, Hang, Chunhua, Zhu, Yichao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207206/
https://www.ncbi.nlm.nih.gov/pubmed/32411507
http://dx.doi.org/10.7717/peerj.8841
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author Yang, Yongbo
Wang, Jian
Liang, Qun
Wang, Yi
Chen, Xinhua
Zhang, Qingrong
Na, Shijie
Liu, Yi
Yan, Ting
Hang, Chunhua
Zhu, Yichao
author_facet Yang, Yongbo
Wang, Jian
Liang, Qun
Wang, Yi
Chen, Xinhua
Zhang, Qingrong
Na, Shijie
Liu, Yi
Yan, Ting
Hang, Chunhua
Zhu, Yichao
author_sort Yang, Yongbo
collection PubMed
description Moyamoya disease (MMD) is a progressive stenosis at the terminal portion of internal carotid artery and frequently occurs in East Asian countries. The etiology of MMD is still largely unknown. We performed a case-control design with whole-exome sequencing analysis on 31 sporadic MMD patients and 10 normal controls with matched age and gender. Patients clinically diagnosed with MMD was determined by digital subtraction angiography (DSA). Twelve predisposing mutations on seven genes associated with the sporadic MMD patients of Chinese ancestry (CCER2, HLA-DRB1, NSD-1, PDGFRB, PHACTR1, POGLUT1, and RNF213) were identified, of which eight single nucleotide variants (SNVs) were deleterious with CADD PHRED scaled score > 15. Sanger sequencing of nine cases with disease progression and 22 stable MMD cases validated that SNV (c.13185159G>T, p.V265L) on PHACTR1 was highly associated with the disease progression of MMD. Finally, we knocked down the expression of PHACTR1 by transfection with siRNA and measured the cell survival of human coronary artery endothelial cell (HCAEC) cells. PHACTR1 silence reduced the cell survival of HCAEC cells under serum starvation cultural condition. Together, these data identify novel predisposing mutations associated with MMD and reveal a requirement for PHACTR1 in mediating cell survival of endothelial cells.
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spelling pubmed-72072062020-05-14 PHACTR1 is associated with disease progression in Chinese Moyamoya disease Yang, Yongbo Wang, Jian Liang, Qun Wang, Yi Chen, Xinhua Zhang, Qingrong Na, Shijie Liu, Yi Yan, Ting Hang, Chunhua Zhu, Yichao PeerJ Cell Biology Moyamoya disease (MMD) is a progressive stenosis at the terminal portion of internal carotid artery and frequently occurs in East Asian countries. The etiology of MMD is still largely unknown. We performed a case-control design with whole-exome sequencing analysis on 31 sporadic MMD patients and 10 normal controls with matched age and gender. Patients clinically diagnosed with MMD was determined by digital subtraction angiography (DSA). Twelve predisposing mutations on seven genes associated with the sporadic MMD patients of Chinese ancestry (CCER2, HLA-DRB1, NSD-1, PDGFRB, PHACTR1, POGLUT1, and RNF213) were identified, of which eight single nucleotide variants (SNVs) were deleterious with CADD PHRED scaled score > 15. Sanger sequencing of nine cases with disease progression and 22 stable MMD cases validated that SNV (c.13185159G>T, p.V265L) on PHACTR1 was highly associated with the disease progression of MMD. Finally, we knocked down the expression of PHACTR1 by transfection with siRNA and measured the cell survival of human coronary artery endothelial cell (HCAEC) cells. PHACTR1 silence reduced the cell survival of HCAEC cells under serum starvation cultural condition. Together, these data identify novel predisposing mutations associated with MMD and reveal a requirement for PHACTR1 in mediating cell survival of endothelial cells. PeerJ Inc. 2020-05-05 /pmc/articles/PMC7207206/ /pubmed/32411507 http://dx.doi.org/10.7717/peerj.8841 Text en ©2020 Yang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Cell Biology
Yang, Yongbo
Wang, Jian
Liang, Qun
Wang, Yi
Chen, Xinhua
Zhang, Qingrong
Na, Shijie
Liu, Yi
Yan, Ting
Hang, Chunhua
Zhu, Yichao
PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title_full PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title_fullStr PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title_full_unstemmed PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title_short PHACTR1 is associated with disease progression in Chinese Moyamoya disease
title_sort phactr1 is associated with disease progression in chinese moyamoya disease
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207206/
https://www.ncbi.nlm.nih.gov/pubmed/32411507
http://dx.doi.org/10.7717/peerj.8841
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