Phenotype-genotype correlations in patients with TGFBI-linked corneal dystrophies in Taiwan.

purposeTo determine the phenotype-genotype correlations in patients with corneal dystrophies associated with human transforming growth factor-β-induced (TGFBI) mutations at the National Taiwan University Hospital.

methodsTwenty-five affected patients from 15 families with corneal dystrophies were recruited. They underwent slit-lamp biomicroscopy and visual acuity examinations. Genomic DNA was extracted from their peripheral blood, and the exons amplified from TGFBI were sequenced.

resultsEleven patients from 9 families with granular corneal dystrophy (GCD) presented with a wide spectrum of dot or fleck opacities and shared some similar clinical features. Genetic studies revealed an R124H mutation in 5 families and an R555W mutation in 4 families. A patient with GCD type 2 and an R124H mutation showed a marked increase in opacities in the laser-assisted in situ keratomileusis (LASIK) flap interface. Six patients from 3 families with superficial honeycomb opacities had an R555Q mutation. Of the 4 patients from 3 families with variant lattice line opacities, 3 from 2 families had an R124C mutation, whereas 1 from the third family had an A546D mutation. Spontaneous mutations were detected in 2 families: an R124C mutation in 1 family with lattice corneal dystrophy (LCD) type I and an A546D mutation in the other with atypical LCD.

conclusionsIn most cases, TGFBI-linked corneal dystrophies had good phenotype-genotype correlations; however, some phenotypic variation was present. The most common mutations in Taiwan were R124H in GCD type 2 and R555W in GCD type 1. The R555Q mutation in Thiel-Behnke corneal dystrophy is not as rare in Taiwan as it is in other Asian countries. Sequencing of TGFBI can aid in the precise classification of these corneal dystrophies.