Abnormal cone ERGs in a family with congenital nystagmus and photophobia harboring a p.X423Lfs mutation in the PAX6 gene

Abstract

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.

Molecular characterization of a series of 990 index patients with albinism

“…For this reason, we recently included in our panel the X‐linked nystagmus gene FRMD7 (data not shown) and identified a pathogenic FRMD7 variant in one male patient with iris transillumination, retinal hypopigmentation, and congenital nystagmus (data not shown). Other patients may have some other disorder with nystagmus and/or various degrees of foveal hypoplasia, photophobia, fundus hypopigmentation, and visual impairment such as Aland Island eye disease ( CACNA1F gene; Jalkanen et al., ; Wutz et al., ) and atypical PAX6 ‐related phenotypes (Hood, Kerr, Smaoui, & Iannaccone, ; Thomas, Maconachie, Sheth, McLean, & Gottlob, ). Atypical presentations of the various forms of congenital stationary night blindness may also present a clinical overlap with ocular forms of albinism.…”

Early light deprivation effects on human cone‐driven retinal function

“…Full‐field ERG recordings allow noninvasive evaluation of the cone outer retinal function (Hood & Birch ; McCulloch et al. ); by using specific stimulation settings, it is possible to study the slow negative potential displayed after the positive b‐wave peak.…”

Gene dosage manipulation alleviates manifestations of hereditary PAX6 haploinsufficiency in mice

“…Human studies have shown considerable variability in foveal development in patients even with the same PAX6 mutation, with functional variability within each grade of foveal hypoplasia (35). There are also reports of ERG abnormalities in patients with mutations in the PAX6 gene, suggesting that ERG could be a reasonable functional test to objectively assess the response to potential treatments (36). On the other hand, it is well known that opacifications such as marked cataractous lens changes can reduce ERG a and b wave amplitudes (37).…”