PHACTR1 is associated with disease progression in Chinese Moyamoya disease

PeerJ

article

Yongbo Yang¹  Jian Wang²  Qun Liang³  Yi Wang¹  Xinhua Chen¹  Qingrong Zhang¹  Shijie Na¹  Yi Liu⁴  Ting Yan⁵  Chunhua Hang¹  Yichao Zhu⁶ 

[1] Department of Neurosurgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School;Department of Neurosurgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University;Drum Tower Clinical Medical College, Nanjing Medical University;Department of Neurosurgery, West China Hospital, Sichuan University;Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University;Department of Physiology, Nanjing Medical University;State Key Laboratory of Reproductive Medicine, Nanjing Medical University

关键词: Whole-exome sequencing;    Moyamoya disease;    Mutation;    PHACTR1;   

DOI  :  10.7717/peerj.8841

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

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)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.

【 授权许可】

CC BY