Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis

Gong, Bo; Zhang, Houbin; Huang, Lulin; Chen, Yuhong; Shi, Yi; Tam, Peter; Zhu, Xuejun; Huang, Yi; Sundaresan, Periasamy; Li, Xi; Jiang, Linxin; Yang, Jialiang; Lin, Ying; Lü, Fang; Chen, Lijia; Li, Yuanfeng; Leung, Christopher Kai-Shun; Guo, Xianguang; Zhang, Shanshan; Guo, Hao; Wu, Yaqi; Zhou, Tongdan; Shuai, Ping; Tham, Clement C.; Weisschuh, Nicole; Krishnadas, Subbaiah Ramasamy; Mardin, Christian Y.; Reis, André; Jy, Yang; Zhang, Lin; Zhou, Yu; Wang, Ziyan; Qu, Chao; Shaw, Peter X.; Pang, Chi‐Pui; Sun, Xinghuai; Zhu, Weiquan; Li, Dean Yaw; Pasutto, Francesca; Yang, Zhenglin

doi:10.1038/s41436-019-0507-0

Cited by 18 publications

(12 citation statements)

References 35 publications

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“…These filtered variants were then annotated with ANNO-VAR software (see Methods for detailed information) (Table S1). We selected genes that met all three of the following standards as the top candidate genes for FEVR (38). First, candidate genes harbored at least one "disruptive" variant (nonsense, frameshift, or in splice sites) (39).…”

Section: Wes Of Fevr Families Identified Mutations In Ctnna1mentioning

confidence: 99%

Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling

Zhu

Zhao

et al. 2021

Journal of Clinical Investigation

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We identified three heterozygous mutations in CTNNA1 in familial exudative vitreoretinopathy (FEVR) patients, and these mutations resulted in overactivation of Norrin/βcatenin signaling and disruption of the cadherin/catenin complex. • Clinical features of FEVR were reproduced in mice lacking Ctnna1 in vascular endothelial cells and in mice with an endothelial-cell-specific gain-of-function Ctnnb1 allele. • In a large Indian family with FEVR, we identified an LRP5 mutation (p.P848L) that results in overactivation of Norrin/β-catenin signaling, and we observed clinical features of FEVR in the retina of Lrp5 P847L knock-in mice. • The precise regulation of β-catenin activation is critical for normal retinal vascular development. What Are the Clinical Implications? • Because both in-and overactivation of Norrin/β-catenin signaling can cause defective angiogenesis, careful monitoring during drug treatment targeting β-catenin is warranted. • The cadherin/catenin complex has the potential to be a therapeutic target for other neovascular diseases affecting the blood-brain barrier, which contribute to altered brain function and intellectual disability.

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Section: Wes Of Fevr Families Identified Mutations In Ctnna1mentioning

confidence: 99%

Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling

Zhu

Zhao

et al. 2021

Journal of Clinical Investigation

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“…POAG is a multifactorial disorder with various etiologies that is estimated to occur in about 52 million patients in 2020 around the world [8]. During the last few years, considerable efforts have been made to investigate the molecular mechanisms of POAG [21,22]; however, most previous studies have mainly focused on protein-coding genes or miRNAs but not on lncRNAs [21][22][23].…”

Section: Discussionmentioning

confidence: 99%

Identification of lncRNA–miRNA–mRNA regulatory network associated with primary open angle glaucoma

Zhou

Tan

et al. 2020

BMC Ophthalmol

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Background: Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods: Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results: During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion: This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

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“…POAG is a multifactorial disorder with various etiologies that is estimated to occur in about 52 million patients in 2020 around the world [21]. During the last few years, considerable efforts have been made to investigate the molecular mechanisms of POAG [22,23]; however, most previous studies have mainly focused on protein-coding genes or miRNAs but not on lncRNAs [22][23][24].…”

Section: Discussionmentioning

confidence: 99%

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

Zhou

Tan

et al. 2020

Preprint

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Background Primary open angle glaucoma (POAG) is a complicated disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

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Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis

Cited by 18 publications

References 35 publications

Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling

Catenin α 1 mutations cause familial exudative vitreoretinopathy by overactivating Norrin/β-catenin signaling

Identification of lncRNA–miRNA–mRNA regulatory network associated with primary open angle glaucoma

Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

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