A novel variant of granular corneal dystrophy caused by association of 2 mutations in the TGFBI Gene -: R124L and ΔT125-ΛE126

Objective: To characterize the molecular defect in the TGFBI gene in a French family affected with an atypical granular corneal dystrophy. Patients: This family comprises 9 affected individuals across 3 generations without consanguineous marriage. Methods: Light and electron microscopy were used to examine corneal buttons from patients. Exons of the TGFBI gene were amplified by polymerase chain reaction and sequenced directly using an automated method. Restriction digestion analysis and heteroduplex screening were performed to confirm that the mutations identified were not polymorphisms. Results: Round or snowflakes-like deposits that stained red with Masson trichrome and appeared as dense, rod-shaped structures were observed in the most anterior layers of the central stroma. All patients were heterozygous for the R124L mutation and a novel mutation predicting the deletion of 2 amino acid residues-threonine (T) and glutamic acid (E)-at codons 125 and 126. Conclusions: This French family is affected with a novel variant of granular dystrophy that is caused by a molecular defect in the TGFBI gene, reported here for the first time. Clinical Relevance: These 2 mutations cause a novel variant of granular dystrophy that is intermediate in severity between the classical and superficial variant forms.