Comprehensive Assessment of Genetic Variants WithinTCF4in Fuchs' Endothelial Corneal Dystrophy

Abstract

Complete sequencing of the TCF4 genomic region revealed no single causative variant for FECD. The intronic trinucleotide repeat expansion within TCF4 continues to be more strongly associated with FECD than any other genetic variant.

CTG18.1 Expansion is the Best Classifier of Late-Onset Fuchs' Corneal Dystrophy Among 10 Biomarkers in a Cohort From the European Part of Russia

“…A similar situation was found in studies on the occurrence of FECD markers in the American population: In some studies, the ethnicity was not specified. 16,17,19,35 FECD patients hospitalized at the FEMCFSI are mostly from the Central, Southern, and Volga Federal Districts, and thus, these were included in our study. All of these Federal Districts are situated in the European part of Russia, so we specified that we investigated the occurrence of FECD markers in the background population of this part of Russia.…”

“…Marker alleles were not found in 21 FECD patients; thus, exome sequencing for those particular patients is warranted. 18,19,22,35 76.4-77.0 21,26 17.3-34.1 37,40 43.9 41 25.5 42 72…”

“…Association of the intronic single-nucleotide Copyright 2018 The Authors iovs.arvojournals.org j ISSN: 1552-5783 polymorphism (SNP) rs613872 with FECD was discovered in the Genome-Wide Association Study (GWAS) performed by Baratz et al 12 Later, this association was confirmed in a number of studies involving more than a thousand people. [13][14][15][16][17][18][19][20][21] Other SNPs in the TCF4 gene are associated with FECD but to a lesser extent, namely, rs17595731, rs9954153, and rs2286812. 12,14,15 Wieben et al 22 found another important relationship between FECD and the expansion of trinucleotide repeats in the TCF4 gene intron CTG18.1: The expansion of trinucleotide repeats appeared to be a more specific marker of FECD than rs613872 (96% vs. 79%).…”

Fuchs Corneal Dystrophy

“…44 A comprehensive assessment of 1866 genetic variants, with sequencing of the TCF4 coding region, introns, and flanking sequence surrounding the two variants, revealed that no single causative allele correlated with all cases of FCD, but the trinucleotide repeat is the most strongly associated of the two TCF4 variants. 45 Clusterin is a molecular chaperone which plays a role in extracellular matrix interaction and is overexpressed in FCD relative to pseudophakic bullous keratopathy and normal control corneas 46 and has been shown to colocalize in guttae. 47 In the aforementioned Australian cohort exploring association with TCF4, additional SNPs were interrogated and one found to be significant in CLU (rs17466684, p ¼ 0.003) with odds ratio of 1.85.…”

TGC-Repeats im Intron 2 des TCF4-Gens haben eine große Vorhersagekraft bezüglich Fuchs-Hornhautendotheldystrophie

“…Um auszuschließen, dass die Repeat-Expansion und das G-Allel des Polymorphismus rs613872 in Kopplung mit einer Veränderung in codierenden Abschnitten des TCF4-Gens bzw. des ebenfalls nahe der untersuchten genetischen Region liegenden LOXHD1-Gens (das bei Riazuddin et al [12] [14,24,25]. Auch der Polymorphismus rs613872 ist mehrfach mit der Fuchs-Hornhautendotheldystrophie in Zusammenhang gebracht worden [15-18, 24, 25].…”