Purpose: To report the clinical and molecular study of a family with an autosomal dominant stromal granular dystrophy of the cornea caused by a novel and unusual TGFBI gene mutation.
Methods: A complete ophthalmological examination, corneal dystrophy phenotype characterization, PCR amplification, and automated nucleotidic sequencing of exons 4, 11,12, 13, and 14 of the TGFBI gene was carried out on the family. DNA from 40 unrelated ethnically matched healthy individuals were analyzed as controls.
Results: Corneal dystrophy in two sisters was characterized by multiple grayish-white lesions located in the anterior and mid-stroma. Numerous small sized non-coalescent opacities were observed in the peripheral cornea while fewer larger lesions were apparent towards the central part of the cornea. A heterozygous missense mutation, consisting of a G to A transition at nucleotide position 384 in TGFBI exon 4 that predicts a valine (GTT) to isoleucine (ATT) replacement in residue 113 (Val113Ile) of the TGFBI protein was identified.
Conclusions: This is the most 5' located mutation detected so far in subjects with TGFBI-linked corneal dystrophy. Valine 113 is strictly conserved in TGFBI from several species and we suggest that the phenotype observed in these patients is related to the unusual location of the mutation. Our results expand the mutational spectrum in the group of TGFBI-linked corneal dystrophies.