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Allelic mutations in the BIGH3/TGFB1 gene are responsible for a clinically heterogeneous group of corneal dystrophies inherited in an autosomal-dominant manner. At least seven corneal dystrophies are caused by such mutations and strong genotype–phenotype correlations have allowed classification at the genetic level.1–4 Two mutation hotspots exist at codons 124 and 555, and over 95% of granular corneal dystrophy (CDGGI; OMIM no. 121900) cases have been associated with a Arg555Trp mutation.5 Patients typically present in the first decade with discrete, grey–white, “crumb-like” granules in the anterior corneal stroma, with sparing of the peripheral cornea and of the stroma between the opacities. We report a nuclear family with a mutation in BIGH3/TGFB1, causing granular corneal dystrophy. The daughter presented with granular corneal dystrophy caused by a Arg555Trp mutation in exon 12 of BIGH3/TGFB1. Her father also presented with granular corneal dystrophy (but with few corneal opacities) but had no detectable mutation. This family represents the first de novo instance of a mutation in BIGH3/TGFB1 causing granular corneal dystrophy.
The proband, an 18-year-old female, presented to the optician at age 18 with mild photophobia and minimally reduced vision. She had no history of recurrent erosions. On examination she had corrected visual acuities of 6/9 R and L and her corneas demonstrated classical granular corneal dystrophy, with numerous discrete midstromal and anterior stromal whitish opacities that did …