Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F25%3A10497923" target="_blank" >RIV/00216208:11110/25:10497923 - isvavai.cz</a>

Alternative codes found

RIV/00064165:_____/25:10497923

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BBPnxxJ6xJ" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=BBPnxxJ6xJ</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1001/jamaophthalmol.2025.0109" target="_blank" >10.1001/jamaophthalmol.2025.0109</a>

Result language

angličtina

Original language name

Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity

Original language description

Importance: Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. Objective: To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. Design, Setting, and Participants: This retrospective cohort study recruited 894 individuals with FECD at Moorfields Eye Hospital (London) and General University Hospital (Prague) from September 2009 to July 2023. Ancestry was inferred from genome-wide single nucleotide polymorphism array data. CTG18.1 status was determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (&gt;=50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases were exome sequenced. Main Outcomes and Measures: Association between variants in FECD-associated genes, demographic data, and age at first keratoplasty. Results: Within the total cohort (n = 894), 77.3% of patients were Exp+. Most European (668 of 829 [80.6%]) and South Asian (14 of 22 [63.6%]) patients were Exp+. The percentage of female patients was higher (151 [74.4%]) in the Exp- cohort compared to the Exp+ cohort (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P &lt; .001). The median (IQR) age at first keratoplasty of the Exp + patients (68.2 years [63.2-73.6]) was older than the Exp- patients (61.3 years [52.6-70.4]; difference, 6.5 years; 95% CI, 3.4-9.7; P &lt; .001). The CTG18.1 repeat length of the largest expanded allele within the Exp+ group was inversely correlated with the age at first keratoplasty (β, -0.087; 95% CI, -0.162 to -0.012; P = .02). The ratio of biallelic to monoallelic expanded alleles was higher in the FECD cohort (1:14) compared to an unaffected control group (1:94; P &lt; .001), indicating that 2 Exp+ alleles were associated with increased disease penetrance compared with 1 expansion. Potentially pathogenic variants (minor allele frequency, &lt;0.01; combined annotation dependent depletion, &gt;15) were only identified in FECD-associated genes in 13 Exp- individuals (10.1%). Conclusions and Relevance: In this multicenter cohort study among individuals with FECD, CTG18.1 expansions were present in most European and South Asian patients, while CTG18.1 repeat length and zygosity status were associated with modifications in disease severity and penetrance. Known disease-associated genes accounted for only a minority of Exp- cases, with unknown risk factors associated with disease in the rest of this subgroup. These data may have implications for future FECD gene-targeted therapy development.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10600 - Biological sciences

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)

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

JAMA Ophthalmology

ISSN

2168-6165

e-ISSN

2168-6173

Volume of the periodical

143

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

338-347

UT code for WoS article

001445047900001

EID of the result in the Scopus database

2-s2.0-105002301954