Although mutations in PAX6 are a major cause of aniridia, genetic defects in nearby genes, such as TRIM44 or ELP4, have also been reported to cause aniridia.
The PAX6 mRNA significantly lower in patients with aniridia than in unaffected family members in both families, suggesting that the duplication and splice site deletion caused nonsense-mediated mRNA decay.ConclusionsOur study identified two novel PAX6 variants in two families with aniridia and revealed the pathogenicity of the variants; this would expand the variant spectrum of PAX6 and help us better understand the molecular basis of aniridia, thus facilitating genetic counseling.
Unlike the more common dominant and sporadic forms of aniridia, there has been no significant association with PAX6 mutations in individuals with GS and the mode of inheritance of the disease had long been regarded as uncertain.
We analyzed the PAX6 gene in 11 patients with aniridia fulfilling the following inclusion criteria: partial or complete absence of the iris and age < 18 years at the time of diagnosis.
Although none of the deleted genes are obvious candidates for the patient's phenotype, the absence of aniridia in the presence of this deletion in all three family members further delineates the location of the DRR for PAX6.
In mutations with partial loss of pax6 function eye development is initially relatively normal but froglets show an underdeveloped iris, similar to the classic phenotype (aniridia) seen in human patients with PAX6 mutations.
In conclusion, we identified a novel deletion mutation in the PAX6 gene resulting in an abnormal PAX6 COOH-terminal extension in the Chinese family with aniridia.
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.