Ocular Findings in Gillespie-Like Syndrome: Association with a New PAX6 Mutation

Abstract

We herein report a case of atypical Gillespie syndrome associated with bilateral ptosis, exotropia, corectopia, iris hypoplasia, anterior capsular lens opacities, foveal hypoplasia, retinal vascular tortuosity, and retinal hypopigmentation. Neurologic evaluation revealed a mild hand tremor and learning disability, but no ataxia or cerebellar abnormalities on neuroimaging. Sequencing studies revealed a substitution in intron 2 of the PAX6 gene (IVS2 + 2T > A). To our knowledge, this is the first mutation of PAX6 gene reported in association with a Gillespie-like syndrome.

Elliptical anterior iris stromal defects associated with PAX6 gene sequence changes

“…As Batten disease is genotypically and phenotypically distinct from the anterior segment phenotype due to PAX6 abnormalities, and did not segregate with the PAX6 mutation we report, we believe this is a coincidental finding. These two members were mentally challenged with neurological deficits, but they are distinctly different from the Gillespie syndrome phenotype ( possibly related to PAX6 mutations), 10 where a distinctive aniridia variant with a scalloped iris border not seen in our families, which is associated with mental retardation, is seen. Gillespie syndrome is also an autosomalrecessive disorder unlike the autosomal-dominant pattern reported here.…”

Aniridia

“…PAX6 intragenic mutations have been reported in two individuals with phenotypes overlapping Gillespie syndrome, but these cases probably have atypical aniridia. 41,42 The molecular basis of classical Gillespie syndrome is unidentified.…”

Human Brain Evolution: Harnessing the Genomics (R)evolution to Link Genes, Cognition, and Behavior

“…Examples of genes with critical roles in arealization include Emx2 , Pax6 , and COUP-TFI ( Nr2f1 ) (Krubitzer, 2007). Not surprisingly, variation in some of these genes leads to cognitive deficits including schizencephaly ( EMX2 ) (Brunelli et al, 1996; Faiella et al, 1997), or cerebellar ataxia and intellectual disability (Gillespie syndrome; PAX6 ) (Graziano et al, 2007; Ticho et al, 2006). A better understanding of the genes important for arealization in mammalian brain evolution should provide insight into the gene networks underlying higher cognition.…”