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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PeerJ Inc.
2020-05-01
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| author | Yongbo Yang Jian Wang Qun Liang Yi Wang Xinhua Chen Qingrong Zhang Shijie Na Yi Liu Ting Yan Chunhua Hang Yichao Zhu |
| author_facet | Yongbo Yang Jian Wang Qun Liang Yi Wang Xinhua Chen Qingrong Zhang Shijie Na Yi Liu Ting Yan Chunhua Hang Yichao Zhu |
| author_sort | Yongbo Yang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T06:43:19Z |
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| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:43:19Z |
| publishDate | 2020-05-01 |
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| spelling | doaj.art-5fb0a2f1111348898d5fbbf67a18e6f62023-12-03T10:43:20ZengPeerJ Inc.PeerJ2167-83592020-05-018e884110.7717/peerj.8841PHACTR1 is associated with disease progression in Chinese Moyamoya diseaseYongbo Yang0Jian Wang1Qun Liang2Yi Wang3Xinhua Chen4Qingrong Zhang5Shijie Na6Yi Liu7Ting Yan8Chunhua Hang9Yichao Zhu10Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, ChinaDrum Tower Clinical Medical College, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaSafety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, ChinaDepartment of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, ChinaDepartment of Physiology, Nanjing Medical University, Nanjing, Jiangsu, ChinaMoyamoya 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.https://peerj.com/articles/8841.pdfWhole-exome sequencingMoyamoya diseaseMutationPHACTR1 |
| spellingShingle | Yongbo Yang Jian Wang Qun Liang Yi Wang Xinhua Chen Qingrong Zhang Shijie Na Yi Liu Ting Yan Chunhua Hang Yichao Zhu PHACTR1 is associated with disease progression in Chinese Moyamoya disease PeerJ Whole-exome sequencing Moyamoya disease Mutation PHACTR1 |
| 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 | Whole-exome sequencing Moyamoya disease Mutation PHACTR1 |
| url | https://peerj.com/articles/8841.pdf |
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