RESUMO
PURPOSE: To describe the clinical, functional, and genetic findings in a young Caucasian girl and her father, in whom a mutation of the PAX6 gene was identified. METHODS: Detailed histories, eye examinations, and flash electroretinograms (ERGs) were acquired from both patients, and molecular genetic diagnostic testing was performed. Both patients were followed over a 2-year period. RESULTS: At presentation, the proband displayed congenital nystagmus, photophobia, posterior embryotoxon, foveal hypoplasia, and coarse peripheral retinal pigment epithelium mottling. Light-adapted cone-driven ERG responses were delayed and reduced. The father had similar findings, but additionally displayed corneal clouding and pannus, decreased best-corrected visual acuity, and his ERG demonstrated a larger reduction in ERG cone-driven responses. PAX6 testing of the proband revealed a heterozygous mutation in exon 13 resulting in a p.X423Lfs (p.Stop423Leufs) frameshift amino acid substitution, predicting aberrant protein elongation by either 14 or 36 amino acids (p.X423Lext14 or p.X423Lext36) and subsequent disruption of normal protein function. CONCLUSIONS: The p.X423Lfs mutation has previously been described in cases of atypical aniridia, but this is the first report demonstrating abnormal cone-driven ERG responses associated with this particular mutation of the PAX6 gene. ERG abnormalities have been documented in other mutations of the PAX6 gene, and we propose that the retinal pathology causing these ERG abnormalities may contribute to the photophobia experienced by patients with aniridia. Systematic ERG testing can aid in the diagnosis of PAX6-related disorders and may prove to be a useful tool to objectively assess responses to future treatments.