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Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract
Open accessAbstract
MicroRNAs (miRNAs) bind to complementary sequences within the 3' untranslated region (UTR) of mRNAs from hundreds of target genes, leading either to mRNA degradation or suppression of translation. We found that a mutation in the seed region of miR-184 (MIR184) is responsible for familial severe keratoconus combined with early-onset anterior polar cataract by deep sequencing of a linkage region known to contain the mutation. The mutant form fails to compete with miR-205 (MIR205) for overlapping target sites on the 3' UTRs of INPPL1 and ITGB4. Although these target genes and miR-205 are expressed widely, the phenotype is restricted to the cornea and lens because of the very high expression of miR-184 in these tissues. Our finding highlights the tissue specificity of a gene network regulated by a miRNA. Awareness of the important function of miRNAs could aid identification of susceptibility genes and new therapeutic targets for treatment of both rare and common diseases.
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“Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders1–5”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [3]
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“Besides gene dosage abnormalities37,38, single nucleotide substitutions in two miRNA genes have been identified in human diseases: MIR96 mutations in autosomal dominant deafness 50 (#613704) and MIR184 mutations in EDICT syndrome (#614303) and familial and sporadic cases of keratoconus1–5,39.”
From Gain-of-function mutation of microRNA-140 in human skeletal dysplasia (2019) · cites this paper as [3]
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Metadata
- Authors
- Hughes, A. E., Bradley, D. T., Campbell, M., Lechner, J., Dash, D. P., Simpson, D. A., & Willoughby, C. E.
- Affiliations
- Queen's University Belfast (GB)
- Corresponding author
- Hughes, Anne E.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 89
- Issue
- 5
- Pages
- 628-633
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC3213395
- OpenAlex
- W2093992697
- Cited by
- 276
- References
- 33
- Citations by year
- 2026: 8 · 2025: 16 · 2024: 16 · 2023: 11 · 2022: 16 · 2021: 10 · 2020: 21 · 2019: 29 · 2018: 19 · 2017: 27 · 2016: 25 · 2015: 24 · 2014: 16 · 2013: 23 · 2012: 14
- FWCI
- 13.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion, other-oa)
- Funders
- Public Health Agency (EAT/3976/08)
- Topics
- Health Sciences › Medicine › Ophthalmology › Corneal surgery and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- miR-184, anterior polar cataract, miR-205, INPPL1, ITGB4, tissue-specific gene regulation, cornea, lens, genetic susceptibility
- MeSH terms
- Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases, Cataract, Cornea, HeLa Cells, Humans, Keratoconus, Lens, Crystalline, Mutation, Northern Ireland, Organ Specificity, Phosphoric Monoester Hydrolases, Polymorphism, Genetic, Sequence Homology, Nucleic Acid, Case-Control Studies, Sequence Analysis, RNA, 3' Untranslated Regions, MicroRNAs, Integrin beta4, High-Throughput Nucleotide Sequencing
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