Phenotype‐genotype correlation of p.R124S mutation in granular type 1 corneal dystrophy of Tunisian origin

Abstract : Purpose: We report the clinical features and phenotype‐genotype correlation in a large Tunisian family with granular corneal dystrophy type I. Methods: Twenty‐seven members of the Tunisian family underwent a complete ophthalmologic examination. A histopathological examination was performed on corneal specimens of four patients with advanced stage of corneal dystrophy. DNA extraction and direct Sanger sequencing of the exons 4 and 12 of TGFBI gene was performed for forty‐two members. Results: The diagnosis of granular corneal dystrophy type I was clinically and genetically confirmed. Sequencing of exon 4 of TGFBI gene revealed the p.Arg124Ser mutation in heterozygous and in homozygous status in patients with different clinical severity. Visual acuity was severely affected in the homozygous patients leading to a first penetrating keratoplasty at 20 years of age in 3 cases, and at 8 years in one case. Recurrence occurred rapidly, began in the seat the corneal stitches and remained superficial up to 40 years after the graft. In heterozygous cases, visual acuity ranged from 6/10 to 10/10. Corneal opacities were deeper and predominating in the stromal center. Conclusions: Our study describes for the first time phenotype‐genotype correlation in a large Tunisian family with granular corneal dystrophy type I and illustrates clinical presentation of homozygous p.Arg124Ser mutation. These results help to understand pathophysiology of the disease and profile of relapse after keratoplasty.