Dataset Information

Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

ABSTRACT: To investigate the clinical and genetic features of late-onset Fuchs corneal dystrophy (FCD) on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals.Observational, cross-sectional study.A total of 156 individuals born to inhabitants of Tangier Island volunteered to undergo ophthalmic evaluation. Medical history was ascertained prior to examination. All participants underwent anterior segment examination with slit-lamp biomicroscopy. Retroillumination photographs were acquired from affected individuals and the disease severity was compared with individuals from large families ascertained previously. Genomic DNA samples were investigated for the presence of the recently identified risk allele rs613872, an intronic variant of TCF4.Of the 148 examined individuals who were at least 30 years of age, 32 showed the classical symptoms of late-onset FCD (21.6%), providing a minimum prevalence of 11% among individuals over the age of 50 years. Severity was significantly lower compared to 51 cases from unlinked families, among individuals either 50 to 70 or above 70 years of age (P = .05 and P = .01, respectively). Retroillumination photography analyses were suggestive of mild severity when compared with the disease phenotype associated with FCD1- and FCD2-linked families. The rs613872 variant was associated with a higher affectation rate (P = .01), while the wild-type allele was correlated with a higher proportion of subclinical disease (P = .01).In this study population in Tangier, late-onset FCD manifests clinically with a mild phenotype and increased prevalence. The rs613872 variant correlates with increased affectation and a clinical disease phenotype.

SUBMITTER: Eghrari AO

PROVIDER: S-EPMC4154491 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

Eghrari Allen O AO McGlumphy Elyse J EJ Iliff Benjamin W BW Wang Jiangxia J Emmert David D Riazuddin S Amer SA Katsanis Nicholas N Gottsch John D JD

American journal of ophthalmology 20120208 6

<h4>Purpose</h4>To investigate the clinical and genetic features of late-onset Fuchs corneal dystrophy (FCD) on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals.<h4>Design</h4>Observational, cross-sectional study.<h4>Methods</h4>A total of 156 individuals born to inhabitants of Tangier Island volunteered to undergo ophthalmic evaluation. Medical history was ascertained prior to examination. All participants underwent anterior segment examinati ...[more]

PMID: 22321803

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Project description:Fuchs’ endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet’s membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet’s membrane (CE-DM) specimens using the Illumina HumanHT-12 v3.0 expression array. RNA from pools of FECD-affected (n=3 per pool) and individual unaffected (n=3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD.

Dataset Information

Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

Publications

Prevalence and severity of fuchs corneal dystrophy in Tangier Island.

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