PAX6 and isolated aniridia: For those fewer missense patients with more severe iris hypoplasia (grade 5 or 6), the mutations either abolished the PAX6 start codon (c.2T>G, p.[Met1Arg]) or could in reality affect splicing mechanisms with consequent transcript degradation through nonsense-mediated decay, hence, mimicking loss-of-function variants and leading to classical severe aniridia phenotypes (44, 47).