Analysis of TCF8 Gene in Patients With Fuchs Corneal Endothelial Dystrophy

Abstract

Purpose: : The endothelial (posterior) corneal dystrophies, which result from primary endothelial dysfunction, include Fuchs endothelial dystrophy (FECD), posterior polymorphism dystrophy (PPCD) and congenital hereditary endothelial dystrophy (CHED). As they share common pathological features it is possible that a proportion of them could be clinical manifestations of different mutations of the same gene. Accordingly mutations in COL8A2 gene which encodes the alpha 2 (VIII) collagen chain have been identified in both familial and sporadic FECD as well as in a family with PPCD. The aim of our study was to determine whether mutations of the TCF8 gene, recently implicated in posterior polymorphous dystrophy, may also play a role in the development of the more common Fuch’s endothelial corneal dystrophy (FECD).

Methods: : DNA extraction, PCR amplification, and direct sequencing of all 9 exons of the TCF8 gene were performed in seventy-four unrelated Chinese patients (55 females, 19 males) with a diagnosis of late-onset FECD. Ninety-three age and race matched were used as control samples.

Results: : The affected probands ranged in age from 52 - 91 years (mean age 65.1 years) and consisted of 8 patients with familial FECD and 66 with sporadic FECD. We found two mutations in the coding region of TCF8 gene. A novel missense mutation in one patient (1/74) c.2087A>G in exon 7 (Asn696Ser) and a silent mutation in exon 2 c.192T>C (D64D).

Conclusions: : The identification of a novel missense mutation in only one of our patients implies that TCF8 does not play a significant role in the pathogenesis of FECD in a Chinese population.

Keywords: cornea: endothelium • degenerations/dystrophies • genetics