Rare variants in MIR184 are a novel genetic cause of Fuchs endothelial corneal dystrophy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10504064" target="_blank" >RIV/00216208:11110/25:10504064 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/25:10504064
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=y8VWB-eSmU" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=y8VWB-eSmU</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.gim.2025.101562" target="_blank" >10.1016/j.gim.2025.101562</a>
Alternative languages
Result language
angličtina
Original language name
Rare variants in MIR184 are a novel genetic cause of Fuchs endothelial corneal dystrophy
Original language description
Purpose: To identify novel genetic causes of Fuchs endothelial corneal dystrophy (FECD) within a genetically unsolved patient cohort lacking repeat expansions in the TCF4 gene (Exp-). Methods: A rare variant analysis framework (CoCoRV) was applied to exome data, in combination with in silico modeling, luciferase reporter, and RNA-seq analysis to characterize transcriptome-wide consequences of identified variants. Results: A gene burden analysis identified MIR184, a microRNA encoding gene, to be enriched for rare pathogenic variants within the studied Exp-FECD cohort. In total, 2 noncoding rare variants were identified in 4 unrelated FECD probands: NR_029705.1:n.58G>A and n.73G>T. Both variants altered highly conserved mature sequence residues, were predicted to induce hairpin structural changes, and were experimentally determined to disrupt microRNA-mRNA interactions. RNA-seq of transfected human corneal endothelial cells revealed that the mutants elicited distinct transcriptomic profiles. Enriched KEGG pathways included PI3K-Akt signaling, focal adhesion, and immune response, revealing shared pathogenic mechanisms between MIR184-associated FECD and the more common TCF4 repeat expansion-mediated form of disease. Conclusion: MIR184 variants are a novel rare genetic cause of FECD, and common pathways of transcriptomic dysregulation are shared across genetically distinct subtypes of the disease. These pathways may serve as future gene agnostic targets for therapeutic interventions. (c) 2025 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10600 - Biological sciences
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genetics in Medicine
ISSN
1098-3600
e-ISSN
1530-0366
Volume of the periodical
27
Issue of the periodical within the volume
11
Country of publishing house
US - UNITED STATES
Number of pages
12
Pages from-to
101562
UT code for WoS article
001584173100002
EID of the result in the Scopus database
2-s2.0-105016376814