A novel variant of granular corneal dystrophy caused by association of 2 mutations in the TGFBI Gene - R124L and Delta T125-Lambda E126

Objective: To characterize the molecular defect in the TGFBI gene in a Fren ch 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 dige stion analysis and heteroduplex screening were performed to confirm that th e mutations identified were not polymorphisms. Results: Round or snowflakes-like deposits that stained red with Masson tri chrome and appeared as dense, rod-shaped structures were observed in the mo st anterior layers of the central stroma. All patients were heterozygous fo r the R124L mutation and a novel mutation predicting the deletion of 2 amin o acid residues-threonine (T) and glutamic acid (E)-at codons 125 and 126. Conclusions: This French family is affected with a novel variant of granula r dystrophy that is caused by a molecular defect in the TGFBI gene, reporte d here for the first time. Clinical Relevance: These 2 mutations cause a novel variant of granular dys trophy that is intermediate in severity between the classical and superfici al variant forms.