Prevalence and Severity of Fuchs Corneal Dystrophy in Tangier Island

Abstract

Purpose To investigate the clinical and genetic features of late-onset FCD on Tangier, an island in the Chesapeake Bay with an isolated population of approximately 500 individuals. Design Observational, cross-sectional study Methods 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. Results 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 = 0.05 and 0.01, 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=0.01), while the wild-type allele was correlated with a higher proportion of subclinical disease (p=0.01). Conclusions 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.

Comprehensive Assessment of Genetic Variants WithinTCF4in Fuchs' Endothelial Corneal Dystrophy

“…This is the same SNV identified by Baratz et al 13 in a full genome wide association study and subsequently validated by others. [26][27][28][29][30][31][32] Importantly, we did not identify any novel SNVs that appear to be causative for FECD. In particular, none of the top 25 SNVs with the strongest association with disease status resides in the coding region of any of the 48 transcripts produced from this gene (Ensembl).…”

The frequency of occurrence of certain corneal conditions by age and sex in Iranian adults

“…Reported rates in previous studies are similarly low [8,[18][19][20]. For instance, a study in America found only 897 cases of corneal dystrophy among one million people [8].…”

Fuchs Corneal Dystrophy

“…37 The population of Tangier, an island in the Chesapeake Bay with a high prevalence of FCD, was found to also demonstrate a high minor allele frequency of 0.37, comparable to affected cohorts in the aforementioned studies. 38 Globally, findings were replicated in an Australian cohort of 105 cases and 275 controls with odds ratio of 4.05. 39 In a Chinese cohort of 57 affected and 121 unaffected individuals, two other SNPs in TCF4 were significantly associated with FCD affectation with an odds ratio over 2 40 ; however, the rs613872 minor allele was absent among the affected cohort.…”