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Natalie C. Kerr, Nizar Smaoui, Alessandro Iannaccone; Abnormal Cone ERGs In A Family With Congenital Nystagmus, Photophobia, Harboring An X423L Mutation In The PAX6 Gene. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2399.
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To present the clinical, functional and genetic findings in a family presenting with congenital nystagmus and photophobia in two generations, and in which a frameshift PAX6 mutation was discovered.
We investigated a 3-year old Caucasian blond girl (proband) and her father, both presenting with congenital nystagmus and photophobia. Dark- and light-adapted flash electroretinograms (ERGs) were performed on both subjects (under Propofol-induced anesthesia in the proband). Isolate consanguinity between the parents of the proband could not be excluded.
No iris transillumination or defects were seen in either the proband or the father, and intraocular pressure was normal in both. However, both subjects presented with mild anisocoria, mild pupillary ectopia, and bilateral ectropion uveae. In addition, the father exhibited corneal pannus. Flash ERG testing showed reduced but clearly recordable cone-driven responses of normal morphology in both proband and father, inconsistent with achromatopsia, blue-cone monochromacy, or congenital stationary night blindness. An aniridia variant (vs. a cone dystrophy) was suspected, and PAX6 gene mutation analysis was performed. Testing revealed in both subjects a c.1267dupT change of the PAX6 gene, resulting in a p.Stop423Leufs (X423L) mutation, which leads to an abnormally long PAX6 gene product.
The PAX6 X423L frameshift mutation has been previously reported to occur in patients with aniridia and other subtler phenotypes (e.g., Baum et al. 1999; Singh et al. 2001; Hever et al. 2006), but to the best of our knowledge had not been shown before to result in abnormal retinal function as in this family. We are aware of only two other reports of abnormal ERGs in a PAX6-related phenotypes (Wu et al. 1991; Jia et al. 2010). In this family, a selective effect on the cone system was observed. The finding of an abnormal ERG is consistent with the role of PAX6 in retinal development and indicates that systematic ERG studies in PAX6-positive families would seem warranted. Follow-up testing is planned for this family to determine if the observed ERG changes are progressive or purely developmental.
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