PAX6 missense mutation in isolated foveal hypoplasia

Autoregulation of Pax6 transcriptional activation by two distinct DNA‐binding subdomains of the paired domain

“…In this paper, we analysed the mechanism of DNAbinding and transcriptional activation by Pax6, by using the paired domain mutants previously isolated from patients with ocular disorders (Hanson et al 1994;Azuma et al 1996). Extending previous observations (Epstein et al 1994b), we clearly demonstrate that the two subdomains can bind independently to their cognate sites.…”

“…Taken together, the R128C mutation that hyperactivates transcription directed from P6CON and abolishes the transactivation via 5aCON causes a defect of the posterior part of the eye (Azuma et al 1996), while the R26G mutation that reduces the transactivation via P6CON and hyperactivates the transcription directed from 5aCON is associated with a defect in the anterior part (Hanson et al 1994). Another point mutation that occurs in the exon 5a splice acceptor of PAX6 and increases the ratio of Pax6-5a variant has been reported which also causes a defect of the anterior part (Epstein et al 1994b).…”

Continuous expression of the homeobox gene Pax6 in the ageing human retina

“…These disorders range from autosomal dominant keratitis, congenital cataract, Peter's anomaly and aniridia to isolated foveal hypoplasia, [3][4][5][6][7][8][9][10][11] for review see. 14 Furthermore, homozygous human Pax6 mutations lead to anophtalmia, brain malformation, and early postnatal Figure 1 Western blot analysis of PAX6 expression and its alternative splice forms in human retinas at various ages (17,28,36,45,55,66, and 79 years).…”

“…In the last years, a number of human Pax6 mutations have been identified leading to a variety of ocular malformations of the anterior and posterior segment. [3][4][5][6][7][8][9][10][11] In the developing human retina, PAX6 expression can be histochemically detected in the Inner Nuclear Layer and Ganglion Cell Layer, as demonstrated by Nishina et al 12 in human foetuses up to gestation week 22.…”

Aniridia and optic nerve hypoplasia

“…[8][9][10][11] PAX6 mutations have been implicated in multiple congenital ophthalmic abnormalities including isolated foveal hypoplasia, Peters anomaly, corneal dystrophies, and cataracts. 8,[12][13][14] Moreover, PAX6 mutations have been reported to result in a wide variety of congenital optic nerve abnormalities including hypoplasia. 8 Therefore, it seems likely that a PAX6 mutation, resulting in the aniridic phenotype, could be responsible for abnormal optic nerve development.…”