Abstract
Background: To evaluate the distribution of the transforming growth factor-beta induced (TGFBI) corneal dystrophies in a multi-ethnic population in Singapore, and to present the different phenotypes with the same genotype. Methods: This study included 32 patients. Slit lamp biomicroscopy was performed for each patient to determine the disease phenotype. Genomic DNA was extracted from the blood samples and the 17 exons of the TGFBI gene were amplified by PCR and sequenced bi-directionally for genotype analysis. Results: Regarding phenotypes, the study patients comprised 11 (34.4%; 8 with R555W and 3 with R124H mutation) patients with granular corneal dystrophy type 1 (GCD1), 6 (18.8%; 5 with R124H and 1 with R124C mutation) patients with GCD2, 13 (40.6%; 7 with R124C, 2 with H626R, 2 with L550P, 1 with A620D and 1 with H572R) patients with lattice corneal dystrophy (LCD) and 2 (6.3%; 1 with R124L and 1 with R124C) patients with Reis–Bückler corneal dystrophy. Regarding genotype, R124H mutation was associated with GCD2 (5 cases; 62.5%) and GCD1 (3 cases; 37.5%). R124C mutation was associated with LCD (7 cases; 87.5%) and GCD2 (1 case; 12.5%). All the 8 cases (100%) of R555W mutation were associated with GCD1. Conclusions: Although the association between genotype and phenotype was good in most cases (65.7%; 21 of 32 patients), genotype/phenotype discrepancy was observed in a significant number.
Highlights
Corneal dystrophies represent a group of hereditary, bilateral and non-inflammatory conditions characterized by the progressive accumulation of abnormal deposits in different layers of the cornea, which causes corneal opacity and visual impairment [1,2]
Regarding the phenotypes of transforming growth factor-beta induced (TGFBI) corneal dystrophy, the subjects comprised 11 (34.4%) patients with granular corneal dystrophy type 1 (GCD1), 6 (18.8%) patients with granular corneal dystrophy type 2 (GCD2), 13 (40.6%) patients with lattice corneal dystrophy (LCD), 2 (6.3%) patients with Reis–Bücklers corneal dystrophy (RBCD)
Regarding the distribution of TGFBI mutations in each phenotype of corneal dystrophy, patients with GCD1 consisted of 3 patients with R124H and 8 patients with R555W, and those with GCD2 comprised 5 patients with R124H and 1 patient with R124C
Summary
Corneal dystrophies represent a group of hereditary, bilateral and non-inflammatory conditions characterized by the progressive accumulation of abnormal deposits in different layers of the cornea, which causes corneal opacity and visual impairment [1,2]. Munier et al [4] first recognized the associations between the phenotypes and genotypes for corneal dystrophies caused by TGFBI gene mutations, as follows: p.Arg124Leu(R124L) for Reis–Bücklers corneal dystrophy (RBCD), p.Arg555Gln (R555Q) for Thiel-Behnke corneal dystrophy (TBCD), p.Arg555Trp (R555W) for granular corneal dystrophy type 1 (GCD1), p.Arg124His (R124H) for granular corneal dystrophy type 2 (GCD2) and p.Arg124Cys (R124C) for lattice corneal dystrophy type 1 (LCD1) [4]. The IC3D further updated the classification in 2015 that incorporated new clinical, histopathologic and genetic information [7], dividing the dystrophies into epithelial and subepithelial dystrophies, epithelial-stromal TGFBI dystrophies including RBCD, TBCD, GCD1, GCD2 and LCD, stromal dystrophies and endothelial dystrophies, according to the corneal layer primarily involved [7]. Conclusions: the association between genotype and phenotype was good in most cases (65.7%; 21 of 32 patients), genotype/phenotype discrepancy was observed in a significant number
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