Genetic analysis of and in Turkish patients with corneal dystrophies: Five novel variations in .

Purpose: To identify pathogenic variations in () and () genes in Turkish patients with corneal dystrophy (CD).

Methods: In this study, patients with macular corneal dystrophy (MCD; n = 18), granular corneal dystrophy type 1 (GCD1; n = 12), and lattice corneal dystrophy type 1 (LCD1; n = 4), as well as 50 healthy controls, were subjected to clinical and genetic examinations. The level of antigenic keratan sulfate (AgKS) in the serum samples of patients with MCD was determined with enzyme-linked immunosorbent assay (ELISA) to immunophenotypically subtype the patients as MCD type I and MCD type II. DNA was isolated from venous blood samples from the patients and controls. Variations were analyzed with DNA sequencing in the coding region of in patients with MCD and exons 4 and 12 in in patients with LCD1 and GCD1. Clinical characteristics and the detected variations were evaluated to determine any existing genotype-phenotype correlations.

Results: The previously reported R555W mutation in was detected in 12 patients with GCD1, and the R124C mutation in was detected in four patients with LCD1. Serum AgKS levels indicated that 12 patients with MCD were in subgroup I, and five patients with MCD were in subgroup II. No genetic variation was detected in the coding region of for three patients with MCD type II. In other patients with MCD, three previously reported missense variations (c. 1A>T, c.738C>G, and c.631 C>T), three novel missense variations (c.164 T>C, c.526 G>A, c. 610 C>T), and two novel frameshift variations (c.894_895 insG and c. 462_463 delGC) were detected. These variations did not exist in the control chromosomes, 1000 Genomes, and dbSNP.

Conclusions: This is the first molecular analysis of and in Turkish patients with different types of CD. We detected previously reported, well-known hot spot mutations in in the patients with GCD1 and LCD1. Eight likely pathogenic variations in , five of them novel, were reported in patients with MCD, which enlarges the mutational spectrum of MCD.