microRNAs and inherited retinal dystrophies
Open accessAbstract
Inherited retinal dystrophies (IRD) are a heterogeneous group of blinding diseases that affect more than 200,000 Americans and millions worldwide (1). Identification of genes that are responsible for IRD when defective is of great importance to the basic understanding as well as development of efficient gene diagnosis and treatment. Thus far, 272 genetic loci are linked to various forms of IRD; among these, 232 protein-coding genes have been identified to cause IRD when defective (RetNet, https://sph.uth.edu/Retnet, last updated April 29, 2015). microRNAs (miRNAs) are endogenous, small, noncoding, regulatory RNAs (2). Since their discovery in 1993 (3, 4), miRNAs have proven to play important roles in the fine-tuning of gene expression at posttranscriptional levels (2). In spite of their importance in gene-expression regulation, few mutations of individual miRNAs have been found to cause Mendelian inherited diseases in humans, raising doubts about their importance in normal development and functions, and whether mutations in a miRNA can have significant functional impact to cause Mendelian inherited diseases, including IRD. Recently, a point mutation in the seed sequence of miR-184 was reported to cause familial keratoconus with cataract (5) and an anterior-segment dysplasia syndrome with endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (6), suggesting that miR-184 is required for anterior-segment development and function, and proving that mutations in an individual miRNA can cause inherited ocular disease in humans. In mice, Lumayag et al. demonstrated that inactivation of the miR-183/96/182 cluster gene causes syndromic IRD with multisensory defects (7), suggesting that defects in miRNA genes can cause IRD in mammals. However, until now, no mutations in miRNAs have been found to cause IRD in humans. In PNAS, Conte et al. report a dominant mutation in miR-204 that causes IRD associated with ocular coloboma in a large five-generation family (8). This …
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The pathogenic role of miRNAs may have been significantly underestimated and could explain part of the missing heritability.
“In general, the pathogenic role of miRNAs may have been significantly underestimated and could explain part of the missing heritability.22”
From Confirmation of the <i>MIR204</i> n.37C>T heterozygous variant as a cause of chorioretinal dystrophy variably associated with iris coloboma, early-onset cataracts and congenital glaucoma (2023) · cites this paper as [22]
The discussion on p. 2 says miRNA mutations can cause inherited retinal dystrophy and recommends screening for additional disease-causing mutations, supporting the possibility that their contribution has been overlooked. It does not discuss missing heritability or establish that the pathogenic role of miRNAs has been significantly underestimated in general. (LLM, conf=0.79)
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Cites
Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract
Hughes, A. E., Bradley, D. T., Campbell, M., Lechner, J., Dash, D. P., Simpson, D. A., & Willoughby, C. E. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.09.014 · Cited by 276 · see citing works
Soldà, G., Robusto, M., Primignani, P., Castorina, P., Benzoni, E., Cesarani, A., Ambrosetti, U., Asselta, R., & Duga, S. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr493 · Cited by 102 · see citing works
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Research works printed but not linked: 6
- 11 Deo M, Yu JY, Chung KH, Tippens M, Turner DL (2006) Detection of mammalian microRNA expression by in situ hybridization with RNA oligonucleotides. Dev Dyn 235(9):2538 -2548.
- 12 Wang FE, et al. (2010) MicroRNA-204/211 alters epithelial physiology. FASEB J 24(5):1552 -1571.
- 14 Conte I, et al. (2014) The combination of transcriptomics and informatics identifies pathways targeted by miR-204 during neurogenesis and axon guidance. Nucleic Acids Res 42(12): 7793 -7806.
- 15 Shaham O, et al. (2013) Pax6 regulates gene expression in the vertebrate lens through miR-204. PLoS Genet 9(3):e1003357.
- 16 Lewis BP , Shih IH, Jones-Rhoades MW, Bartel DP , Burge CB (2003) Prediction of mammalian microRNA targets. Cell 115(7):787 -798.
- 19 Simon D, et al. (2010) A mutation in the 3 ′ -UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia. Hum Mol Genet 19(10):2015 -2027.
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Jedlickova, J., Vajter, M., Barta, T., Black, G., Mares, J., Fichtl, M., Kousal, B., Dudakova, L., & Liskova, P. (2023) · doi:10.1101/2023.02.09.23284763
- Authors
- Xu, S.
- Affiliations
- Wayne State University (US)
- Corresponding author
- Xu, Shunbin
- ORCID
- Xu, Shunbin
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-07-09
- Volume
- 112
- Issue
- 29
- Pages
- 8805-8806
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4517244
- OpenAlex
- W1557411537
- Cited by
- 12
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2020: 1 · 2019: 3 · 2017: 1 · 2016: 1
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- microRNA, inherited retinal disease, retinal disease, gene expression regulation, microRNA expression
- MeSH terms
- Coloboma, Female, Humans, Male, MicroRNAs, Retinal Dystrophies
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