Abstract
Abstract: :
Purpose:To report the discovery of two spontaneous mutations in the TGFBI gene that led to granular corneal dystrophy type III (GCD III). Methods:Two unrelated children, diagnosed with a corneal dystrophy in the absence of a positive family history of a corneal disorder, were studied clinically and genetically. Family histories and pedigrees were compiled. All available clinical records and photographs were reviewed. Corneal tissue obtained at biopsy in one individual for diagnostic purposes was examined. Blood samples or buccal scrapings from the unaffected parents and the affected children were gathered and the DNA was extracted. A mutational analysis of the TGFBI gene was performed via PCR amplification and subsequent nucleotide sequence analysis. The maternity and paternity of both affected children were investigated through DNA analysis of 15 alleles to confirm that the mother and father of each of the children were indeed their biological parents. Results:An evaluation of the families of the two children indicated that they were not related to each other. Cornea specialists at two major university clinics made the clinical diagnosis of Reis–Bücklers dystrophy (GCD III) in the children. Clinical records and photographs confirmed this impression. Age of onset was twelve months in one child and eighteen months in the other. Symptoms and signs included recurrent corneal erosions, painful episodes, and photophobia. Clinical examination revealed epithelial haze and decreased tear film. Both affected individuals were found to have a nucleotide substitution of guanine for thymine at position 371 in exon 4 of the TGFBI gene, which is predicted to change the amino acid arginine to leucine at codon 124 (R124L). The parents of both affected individuals were normal in exon 4. DNA allelic analysis of affected individuals and their parents confirmed that the mother and father of both affected individuals were the biological parents. Conclusions:To the best of our knowledge this is the first report of a spontaneous R124L mutation in the TGFBI gene causing GCD III. These two unrelated cases of GCD III further confirm the utility of combining genetic analyses with clinical acumen in the diagnosis of corneal disease.
Keywords: genetics • cornea: clinical science • pathology: human