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Cited by 108Ocular Disorders and TreatmentsMicroRNA in disease regulationRetinal Development and Disorders

A Single-Base Substitution in the Seed Region of miR-184 Causes EDICT Syndrome

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Iliff, Benjamin W., Riazuddin, S. Amer, Gottsch, John D.·2012·Investigative Opthalmology & Visual Science
DOI 10.1167/iovs.11-8783PMC PMC3292370
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Abstract

PURPOSE: To investigate the cause of the syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT). METHODS: Previously a multigenerational family was reported that comprised 10 individuals affected by syndromal anterior segment dysgenesis. Blood samples were re-collected from eight affected and two unaffected individuals, and genomic DNA was extracted. A total of 24 candidate genes and 4 microRNAs residing within the critical interval were sequenced bidirectionally. In silico analyses were performed to examine the effect of the causal variant on the stability of the pre-microRNA structure. RESULTS: Bidirectional sequencing identified the single-base substitution +57C>T in miR-184. This variation segregated with the disease phenotype and was absent in the 1000 Genomes project, 1130 control chromosomes, and 28 nonhuman vertebrates. CONCLUSIONS: The single-base-pair substitution in the seed region of miR-184 is responsible for the disease phenotype observed in EDICT syndrome.

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  • Heterozygous loss-of-function point mutations of miRNA genes are associated with several human congenital disorders.

    “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 [4]

    The Results (page unavailable) identify a heterozygous single-base substitution in miR-184 that segregates with EDICT syndrome, which includes congenital cataract. The Discussion (page unavailable) proposes reduced miR-184 expression or activity as possible mechanisms but does not establish loss of function. This paper provides one example, not evidence for several congenital disorders. (LLM, conf=0.86)

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  • Besides gene dosage abnormalities, single nucleotide substitutions in two miRNA genes have been identified in human diseases: MIR96 mutations in autosomal dominant deafness 50 and MIR184 mutations in EDICT syndrome and familial and sporadic cases of keratoconus.

    “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 [4]

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Cited by

Sorted by citations

Authors
Iliff, B. W., Riazuddin, S. A., & Gottsch, J. D.
Affiliations
Johns Hopkins University (US)
Venue
Investigative Opthalmology & Visual Science
Publisher
Association for Research in Vision and Ophthalmology (ARVO)
Published
2012-01-25
Volume
53
Issue
1
Pages
348
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
DOI
10.1167/iovs.11-8783
PMC
PMC3292370
OpenAlex
W2022133540
Cited by
108
References
1
Citations by year
2026: 2 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 6 · 2017: 11 · 2016: 7 · 2015: 16 · 2014: 6 · 2013: 9 · 2012: 7
FWCI
4.39
Type
journal article
Language
en
Open access
Locations
  • Investigative Ophthalmology & Visual Science (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Eye Institute (R01EY016835)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Ocular Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
Keywords
miR-184, single base substitution, endothelial dystrophy, iris hypoplasia, congenital cataract
MeSH terms
Cataract, Corneal Dystrophies, Hereditary, Corneal Stroma, Endothelium, Corneal, Eye Abnormalities, Female, Gene Expression Regulation, Humans, Iris, Male, Pedigree, Phenotype, Syndrome, Gene Library, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, MicroRNAs

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