Prevalence of TCF4 Triplet Repeat Expansion Associated with Fuchs’ Endothelial Corneal Dystrophy in the United States and Global Populations DOI Creative Commons
Xunzhi Zhang, Ashwani Kumar, Xin Gong

и другие.

Ophthalmology Science, Год журнала: 2024, Номер 5(1), С. 100611 - 100611

Опубликована: Авг. 30, 2024

ObjectiveAn intronic CTG triplet repeat expansion in the transcription factor 4 gene (TCF4) (CTG18.1) confers significant risk for development of Fuchs' endothelial corneal dystrophy (FECD). The objective this study was to conduct an unbiased survey CTG18.1 allele frequencies a multi-ethnic, population-based cohort from United States and global populations.DesignCross-sectional studySubjectsDallas Heart Study (DHS) including 1,599 African Americans (AAs), 1,028 European (EAs), 458 Latinos; 2,500 individuals 1000 Genomes Project (1KGP) sampled 26 populations across 5 continents.MethodsWe genotyped short tandem DHS using targeted polymerase chain reaction amplification followed by fragment analysis. We also inferred genotype based on short-read whole-genome sequencing 1KGP computational tool ExpansionHunter.Main Outcome MeasuresThe prevalence expanded with ≥40 repeats determined U.S. populations.ResultsThe carrier rates were 3.1%, 8.1%, 3.3% AAs, EAs, Latinos, respectively, DHS, 2.7%, 9.5%, 5.2%, 7.2%, 5.2% (AFR), (EUR), East Asian (EAS), South (SAS), admixed American (AMR) continental populations, 1KGP. distributions are similar. median length ∼17 interquartile range (IQR) between 12 23 populations. ∼19 all IQR 13 26. highest carriers ranging 12.1% 12.5% observed some EUR AMR subpopulations. frequency alleles absent or low (0 - 1.9%) subpopulations Africa but present at 6.2% Kenyan subpopulation West Africa.ConclusionsThe TCF4 is most prevalent people ancestry least ancestry, which consistent FECD prevalence. common disease-causing humans worldwide implications disease.

Язык: Английский

Characterisation of the role played by ELMO1, GPR141 and the intergenic polymorphism rs918980 in Fuchs' dystrophy in the Indian population DOI Creative Commons

S. K. Sharma,

Samar Basak, Sujata Das

и другие.

FEBS Open Bio, Год журнала: 2025, Номер unknown

Опубликована: Фев. 19, 2025

Fuchs' endothelial corneal dystrophy (FECD) is the most common type of primary and can result in transplantation. Here, we investigated genetic association SNP rs918980 (A>G) with FECD role its surrounding genes ELMO1 GPR141 . First, 128 patients 379 controls were genotyped by Sanger sequencing. Our results show that significantly associated Indian population. Furthermore, silico analysis suggested 150 bp region could regulate transcriptional activities nearby genes. Thus, assessed whether differentially expressed tissue a UVA‐induced mice model. Both upregulated western blots studies concluded protein levels also higher endothelium UVA‐exposed eye compared to control eye. Taken together, our suggest might play significant progression. However, further are required better characterize possible regulation

Язык: Английский

Процитировано

0
Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity DOI
Siyin Liu, Amanda N. Sadan, Nihar Bhattacharyya

и другие.

JAMA Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

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

Язык: Английский

Процитировано

0
Genotype–Phenotype Correlations in Corneal Dystrophies: Advances in Molecular Genetics and Therapeutic Insights DOI Creative Commons
Petra Lišková, Pavlína Skalická, Ľubica Ďuďáková

и другие.

Clinical and Experimental Ophthalmology, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

ABSTRACT Corneal dystrophies are a group of predominantly rare inherited disorders. They by definition bilateral, relatively symmetrical, and without systemic involvement, affecting corneal transparency and/or refraction. Traditional classification is based on slit‐lamp appearance, affected layer histological features. Molecular genetics has provided ultimate proof for the existence distinct discarded duplicates in their terminology. Currently, there at least 16 genes with identified pathogenic variants implicated dystrophies. Herein, we summarise contemporary knowledge genotype–phenotype correlations dystrophies, including critical review some reported variants, along understanding underlying dystrophic process; essential development targeted therapies.

Язык: Английский

Процитировано

0
HeterozygousCOL17A1variants are a frequent cause of amelogenesis imperfecta DOI
Tero Kivelä,

Walter Lisch,

Jayne E Weiss

и другие.

Journal of Medical Genetics, Год журнала: 2024, Номер unknown, С. jmg - 110310

Опубликована: Авг. 30, 2024

Язык: Английский

Процитировано

1
Insights into the causes and consequences of DNA repeat expansions from 700,000 biobank participants DOI Open Access
Margaux L.A. Hujoel, Robert E. Handsaker, Nolan Kamitaki

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 26, 2024

Abstract Expansions and contractions of tandem DNA repeats are a source genetic variation in human populations tissues: some expanded cause inherited disorders, also somatically unstable. We analyzed sequence data, derived from the blood cells >700,000 participants UK Biobank All Us Research Program, developed new computational approaches to recognize, measure learn DNA-repeat instability at 15 highly polymorphic CAG-repeat loci. found that expansion contraction rates varied widely across these loci, even for alleles same length; different loci exhibited variable relative propensities mutate germline versus blood. The high somatic TCF4 enabled genome-wide association analysis identified seven which variants modulate repeat cells. Three implicated contained genes ( MSH3 , FAN1 PMS2 ) Huntington’s disease age-at-onset as well HTT blood; however, specific their effects (instability-increasing or-decreasing) appeared be tissue-specific repeat-specific, suggesting mutation tissues—or tissue—proceeds independently under control substantially variation. Additional modifier included damage response ATAD5 GADD45A . Analyzing expansions together with clinical data showed 5’ UTR glutaminase GLS) gene associated stage 5 chronic kidney (OR=14.0 [5.7–34.3]) liver diseases (OR=3.0 [1.5–5.9]). These other results point dynamics lifespan.

Язык: Английский

Процитировано

1
Advancements in Corneal Transplantation: Addressing Rejection Risks, Innovations and Challenges DOI Creative Commons
Daria Ziemińska,

Karina Motolko,

Rafał Burczyk

и другие.

Quality in Sport, Год журнала: 2024, Номер 35, С. 56443 - 56443

Опубликована: Дек. 16, 2024

Introduction and Objective: Corneal transplantation is an increasingly common surgical procedure, with lamellar keratoplasty now favored over penetrating due to its advantages in outcomes precision. Review methods: A literature review utilizing databases like Scopus, Google Scholar, PubMed, keywords such as "corneal rejection" "high risk of rejection," underscores the need for advancements understanding managing graft rejection. Brief knowledge status: Key insights highlight importance deeper exploration into immunological mechanisms rejection refine therapeutic strategies. The development bioengineered materials acellular porcine corneal stroma (APCS) offers a promising solution global donor shortage, though further validation their clinical utility needed. Complementary therapies amniotic membrane show promise mitigating failure treating surface disorders anti-inflammatory regenerative properties. Moreover, comparative studies suggest that advanced techniques, Descemet Membrane Endothelial Keratoplasty (DMEK), may achieve lower rates compared alternatives Stripping Automated (DSAEK). Discussion: Future priorities include advancing drug delivery systems, ensuring feasibility accessibility materials, conducting large-scale multicenter trials validate novel treatments methods across diverse populations. Summary: Addressing these challenges particularly crucial high-risk pediatric patients, ultimate goal reducing necessity repeat interventions.

Язык: Английский

Процитировано

1
Prevalence of TCF4 Triplet Repeat Expansion Associated with Fuchs’ Endothelial Corneal Dystrophy in the United States and Global Populations DOI Creative Commons
Xunzhi Zhang, Ashwani Kumar, Xin Gong

и другие.

Ophthalmology Science, Год журнала: 2024, Номер 5(1), С. 100611 - 100611

Опубликована: Авг. 30, 2024

ObjectiveAn intronic CTG triplet repeat expansion in the transcription factor 4 gene (TCF4) (CTG18.1) confers significant risk for development of Fuchs' endothelial corneal dystrophy (FECD). The objective this study was to conduct an unbiased survey CTG18.1 allele frequencies a multi-ethnic, population-based cohort from United States and global populations.DesignCross-sectional studySubjectsDallas Heart Study (DHS) including 1,599 African Americans (AAs), 1,028 European (EAs), 458 Latinos; 2,500 individuals 1000 Genomes Project (1KGP) sampled 26 populations across 5 continents.MethodsWe genotyped short tandem DHS using targeted polymerase chain reaction amplification followed by fragment analysis. We also inferred genotype based on short-read whole-genome sequencing 1KGP computational tool ExpansionHunter.Main Outcome MeasuresThe prevalence expanded with ≥40 repeats determined U.S. populations.ResultsThe carrier rates were 3.1%, 8.1%, 3.3% AAs, EAs, Latinos, respectively, DHS, 2.7%, 9.5%, 5.2%, 7.2%, 5.2% (AFR), (EUR), East Asian (EAS), South (SAS), admixed American (AMR) continental populations, 1KGP. distributions are similar. median length ∼17 interquartile range (IQR) between 12 23 populations. ∼19 all IQR 13 26. highest carriers ranging 12.1% 12.5% observed some EUR AMR subpopulations. frequency alleles absent or low (0 - 1.9%) subpopulations Africa but present at 6.2% Kenyan subpopulation West Africa.ConclusionsThe TCF4 is most prevalent people ancestry least ancestry, which consistent FECD prevalence. common disease-causing humans worldwide implications disease.

Язык: Английский

Процитировано

0