In humans, PAX6 is located in chromosome 11p13, and its mutations lead to a variety of hereditary ocular malformations of the anterior and posterior segment, among which aniridia and most probably foveal hypoplasia are the major signs.
Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments.
The NR2E1 coding region, 5' and 3' untranslated regions (UTRs), exon flanking regions including consensus splice sites, and six evolutionarily conserved non-coding candidate regulatory regions were analyzed by sequencing 58 probands with aniridia of whom 42 were negative forPAX6 mutations.
The PAX6 gene, which is mutated in the murine Small eye and human aniridia developmental defects, also encodes a second protein with a 14-amino-acid insertion in the paired domain.
Human mapping studies have shown that the aniridia (AN2) gene, which is part of the Wilms tumor susceptibility, aniridia, genitourinary abnormalities, and mental retardation (WAGR) complex, is also between FSHB and CAT on human chromosome 11.
Heterozygous PAX6 gene mutations leading to haploinsufficiency are the main cause of congenital aniridia, a rare and progressive panocular disease characterized by reduced visual acuity.
Here, we used nonsense suppression to manipulate Pax6 dosage at different developmental times in the eye of the small eye (Pax6<sup>Sey/+</sup>; G194X) mouse model of aniridia.
The internal control was from a girl with typical aniridia and an identified c.718C>T (p.R240X) mutation in PAX6, suggesting the c.608G>A variation in SIX6 was unlikely to play a role in her ocular phenotype.
In particular, we have taken advantage of the development of high-throughput approaches to screen the upstream and downstream regulatory regions of PAX6 in 47 aniridia patients without identified mutation in the coding sequence.
Mutations in paired box gene 6 (PAX6) are the major cause of aniridia that may associate with several other developmental anomalies of the eye, including microcornea in rare cases.