Genotype and phenotype correlation of monogenic corneal dystrophies in population of central Poland

Purpose To assess the genotype-phenotype correspondence in monogenic corneal dystrophies caused by KRT,TGFBI and UBIAD1 genes mutation. Methods 61 patients from 30 Polish families with clinically diagnosed epithelial and stromal corneal dystrophies participated in the study. Corneal phenotypes were assessed by slit lamp, AS-OCT,and confocal microscopy in vivo. Genomic DNA was obtained from blood samples and respective exons (hot spots) were PCR amplified and sequenced on both strands. Results Molecular genetic testing revealed heterozygous missense p.E498V mutation (exon 7) of KRT3 in one family with Meesmann corneal dystrophy phenotype, p.R555W (exon 12) mutation in 19 patients diagnosed with granular type I dystrophy (GCD1). In two patients p.R124H mutation (GCD2, Avellino) was found. In three patients (2 families) heterozygous p.R124L (exon 4) mutation was identified and diagnosed as Reis-Buecklers dystrophy. In two unrelated patient p.R555Q (exon 12) mutation typical for Thiel-Behnke dystrophy was found. Heterozygous p.R124C (exon 4), p.T538R (exon 12) and p.H626R (exon 14) mutations were identified, respectively, in 10 patients diagnosed with lattice corneal dystrophy (LCD1). A novel p.L565P mutation was found in one family with late-onset LCD. Among 18 idividuals (4 families) suffering from stromal Schnyder corneal dystrophy (SCD) molecular genetic testing revealed 3 different UBIAD1 gene mutations: p.N102S, p.D112N, p.T120R. Conclusions The genotype typical for monogenic corneal dystrophies caused by KRT and UBIAD1 genes mutation corresponds with its clinical phenotype. TGFBI is associated with phenotype heterogenity and in some cases only genetic tests may confirm the proper diagnosis. This indicates that a relatively straightforward molecular analysis can be a practical use in diagnosis of these conditions and associated genetic counseling.