Genetics of Refraction and Myopia

Zhang, Qingjiong

doi:10.1016/bs.pmbts.2015.05.007

Cited by 38 publications

(30 citation statements)

References 81 publications

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“…MAPK10 may be downregulated by the upregulated miRNAs, affecting the MAPK cascade in myopia. Besides, abnormal expression of key genes at the transcriptional level may lead to the progression of myopia [7] . In this study, we observed an enrichment of the upregulated miRNAs (miR-15a, miR-16-1, miR-294, miR-466c-5p, miR-466h-5p, miR-468, and miR-699e) in transcription-related biological processes.…”

Section: Functional Annotation Resultsmentioning

confidence: 99%

“…Alteration in gene expression is an important factor leading to the development of refractive errors, and the identification of the genes involved can help elucidate the underlying molecular mechanisms [7] , such as myopiaassociated WNT7B (wingless-type MMTV integration site family, member 7B) [8] . Recently, microRNAs (miRNAs), small, endogenous, noncoding RNAs downregulating target genes at the posttranscriptional level [9] , have been found to be associated with ocular growth manipulation in myopia or other eye diseases [10] .…”

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confidence: 99%

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Potentially Important MicroRNAs in Form-Deprivation Myopia Revealed by Bioinformatics Analysis of MicroRNA Profiling

Mei

Wang²,

Chen³

et al. 2017

Ophthalmic Res

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Objective: This study aimed to identify differentially expressed microRNAs (miRNAs) and to explore their potential roles in form-deprivation myopia. Methods: The microarray data set GSE58124 of miRNAs was downloaded from the Gene Expression Omnibus, and form-deprivation myopia was induced in C57BL/6J mice over the right eye; the contralateral, left eyes were used as controls. Differential expression analysis was done using the LIMMA package. miRDB was used to predict targets for miRNAs. The target genes were put into DAVID to identify significant pathways and biological processes of miRNAs. A functionally collaborative network was constructed using Cytoscape. Result: In total, 24 and 20 upregulated miRNAs, respectively, were screened out in retina and whole-eye tissue. However, there was no dramatic expression change of miRNAs in sclera tissue. By taking intersections, 8 common upregulated miRNAs were obtained in both the retina and the whole-eye samples. According to miRDB, 1,805 target genes were screened out for the 8 differentially expressed miRNAs, including MAPK10 (mitogen-activated protein kinase 10). The functionally collaborative network revealed that “regulation of transcription” was significantly enriched. The pathways “Axon guidance” and “TGF-β signaling pathway” were also enriched. Importantly, miR-466h-5p and miR-466j were significantly enriched in some synaptic transmission-related biological processes. Conclusion: This study identified an upregulation of 8 miRNAs, which may function by disturbing their enriched pathways or biological processes in the progression of myopia.

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Section: Functional Annotation Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Potentially Important MicroRNAs in Form-Deprivation Myopia Revealed by Bioinformatics Analysis of MicroRNA Profiling

Mei

Wang²,

Chen³

et al. 2017

Ophthalmic Res

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“…To build the gene coexpression and genetic interaction networks, we reviewed the PubMed database to look for candidate genes related to nanophthalmos, 31 microphthalmia, anophthalmia, and coloboma (MAC), [32][33][34] high hyperopia, 35 angle-closure glaucoma, 36 and AL 37 ( Supplementary Table S8). Coexpression and genetic interaction networks were created and visualized by GeneMANIA in the Cytoscape program.…”

Section: Gene Coexpression and Genetic Interaction Network Analysesmentioning

confidence: 99%

Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study

Guo

Zhao

Chen

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Citation: Guo C, Zhao Z, Chen D, et al. Detection of clinically relevant genetic variants in Chinese patients with nanophthalmos by trio-based wholegenome sequencing study. Invest Ophthalmol Vis Sci. 2019;60:2904-2913. https://doi.org/10.1167 PURPOSE. Nanophthalmos is a rare genetic disorder commonly characterized by a short axial length (AL) and severe hyperopia. Mutations that have been identified through Mendelian genetic analysis can only explain a fraction of nanophthalmic cases. We investigate the clinically relevant genetic variants in nanophthalmos by whole-genome sequencing (WGS), including de novo mutations (DNMs) and inherited mutations. METHODS.Clinically relevant genetic variants of 11 trios (11 nanophthalmic probands and their unaffected parents) from the Zhongshan Ophthalmic Center, China, were analyzed by WGS. We further screened three trios and 10 sporadic cases to identify the MYRF mutations.RESULTS. In two of 11 trios, without evidence of the presence of deleterious inherited autosomal variants, two DNMs of MYRF (c.789delC, p.S264fs and c.789dupC, p.S264fs) were identified in the probands. These loss-of-function DNMs were predicted to result in premature stop codons and protein structure damage in both probands. In addition, deleterious inherited genetic variants in PRSS56 and MFRP were found in eight probands of the other nine trios. Expanded screening found an additional MYRF DNM (c.1433G>C, p.R478P) in one trio and a stop-gain MYRF mutation (c.2956C>T, p.R986X) in one sporadic case, suggesting the recurrence of MYRF mutations in nanophthalmic patients.CONCLUSIONS. This is the first trio-based WGS study for nanophthalmos, revealing the potential role of DNMs in MYRF and rare inherited genetic variants in PRSS56 and MFRP. The underlying mechanism of MYRF in the development of nanophthalmos needs to be further investigated.

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“…It is a frequent cause of blindness because of the complications, including cataract, glaucoma, vitreous anomaly, and retinal tears or retinal detachment. Genetic factors on high myopia have been confirmed by a number of studies, both on Mendelian traits of early‐onset high myopia (eoHM) and on complex traits of late‐onset high myopia 5,6,7 …”

Section: Introductionmentioning

confidence: 99%

A novel deep intronic COL2A1 mutation in a family with early‐onset high myopia/ocular‐only Stickler syndrome

Sun

Xiao

et al. 2020

Ophthalmic Physiologic Optic

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Citation information: Sun W, Xiao X, Li S, Jia X, & Zhang Q. A novel deep intronic COL2A1 mutation in a family with early-onset high myopia/ ocular-only Stickler syndrome. Ophthalmic Physiol Opt 2020; 40: 281-288. https://doi. AbstractPurpose: To identify the genetic defect causing early-onset high myopia (eoHM)/ ocular-only Stickler syndrome (ocular-STL) in a large Chinese family. Methods: Genomic DNA and clinical data from a four-generation family with eoHM/ocular-STL were collected. Whole-exome sequencing was performed on one affected member in initial screening. Linkage scan based on microsatellite markers was carried out initially from candidate loci associated with autosomal dominant eoHM and Stickler syndrome. Sanger sequencing was used to detect potential variants. The pathogenicity of candidate variants was evaluated using mini genes ex vivo. Results: Eight patients and five unaffected members in the family participated in the study, in which the patients had high myopia with other variable ocular phenotypes but without extraocular abnormalities. Whole exome sequencing did not detect any potential pathogenic variant in all genes known to associate with the disease. The eoHM/ocular-STL in the family was mapped to markers around COL2A1 by candidate loci linkage scan, with a maximum lod score of 3.31 for D12S1590 at θ = 0. A novel deep intronic variant, c.86-50C > G in intron 1 of COL2A1, was detected by Sanger sequencing and co-segregated with eoHM/ocular-STL in the family. Ex vivo splicing test using mini genes confirmed that the variant created a new splicing acceptor 49 bp before the canonical splicing site of exon 2, resulted in addition of 49 bp fragment in the transcript (from c.86-49 to c.86-1) and premature termination. Conclusions: Linkage study, bioinformatics prediction, and ex vivo transcript analysis suggest a novel deep intronic variant adjacent to 5-prime of exon 2 of COL2A1, affecting exon 2 splicing, as a potential cause of ocular-STL in a large family. To our knowledge, this is the first report of an intronic variant around exon 2 as a cause of ocular-STL while a series of variants in the coding region of exon 2, a dispensable alternative-splicing exon for extraocular tissues, in COL2A1 have been reported to cause Stickler syndrome-related ocular phenotype alone.

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Genetics of Refraction and Myopia

Cited by 38 publications

References 81 publications

Potentially Important MicroRNAs in Form-Deprivation Myopia Revealed by Bioinformatics Analysis of MicroRNA Profiling

Potentially Important MicroRNAs in Form-Deprivation Myopia Revealed by Bioinformatics Analysis of MicroRNA Profiling

Detection of Clinically Relevant Genetic Variants in Chinese Patients With Nanophthalmos by Trio-Based Whole-Genome Sequencing Study

A novel deep intronic COL2A1 mutation in a family with early‐onset high myopia/ocular‐only Stickler syndrome

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