Mutant RAMP2 Causes Primary Open-Angle Glaucoma Via the CRLR-Camp Axis
© American College of Medical Genetics and Genomics ARTICLE Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis Bo Gong, PhD1,2, Houbin Zhang, PhD1, Lulin Huang, PhD1, Yuhong Chen, MD3, Yi Shi, PhD1, Pancy Oi-Sin Tam, MS4, Xianjun Zhu, PhD1, Yi Huang, MD1,5, Bo Lei, PhD6, Periasamy Sundaresan, PhD7, Xi Li, MS1, Linxin Jiang, MS1, Jialiang Yang, MS1, Ying Lin, MS1, Fang Lu, PhD1, Lijia Chen, MRCSEd (Ophth), PhD4, Yuanfeng Li, MS1, Christopher Kai-Shun Leung, MD4, Xiaoxin Guo, MS1, Shanshan Zhang, MS1, Guo Huang, MS1, Yaqi Wu, MS1, Tongdan Zhou, MS1, Ping Shuai, PhD1, Clement Chee-Yung Tham, FRCOphth4, Nicole Weisschuh, PhD8, Subbaiah Ramasamy Krishnadas, MD7, Christian Mardin, MD9, André Reis, PhD10, Jiyun Yang, MD1, Lin Zhang, PhD1,3, Yu Zhou, PhD1, Ziyan Wang, PhD1, Chao Qu, MD11, Peter X. Shaw, PhD12, Chi-Pui Pang, DPhil4, Xinghuai Sun, MD3, Weiquan Zhu, MD5, Dean Yaw Li, MD5, Francesca Pasutto, PhD10 and Zhenglin Yang, MD, PhD1,2 Purpose: Primary open-angle glaucoma (POAG) is the leading 4763 POAG patients, whereas no variants were detected in any cause of irreversible blindness worldwide and mutations in known exon of RAMP2 in 10,953 control individuals. Mutant RAMP2s genes can only explain 5–6% of POAG. This study was conducted aggregated in transfected cells and resulted in damage to the AM- to identify novel POAG-causing genes and explore the pathogenesis RAMP2/CRLR-cAMP signaling pathway. Ablation of one Ramp2 of this disease. allele led to cAMP reduction and retinal ganglion cell death in mice. Methods: Exome sequencing was performed in a Han Chinese Conclusion: This study demonstrated that disruption of RAMP2/ cohort comprising 398 sporadic cases with POAG and 2010 CRLR-cAMP axis could cause POAG and identified a potential controls, followed by replication studies by Sanger sequencing.
[Show full text]