PAX6 and isolated aniridia: More recently, this property has been quantified with a haploinsufficiency metric by the Exome Aggregation Consortium (ExAC) (Lek et al. 2016), with an impressive probability of loss-of-function intolerance score, pLI, of 1.00 for PAX6. Whilst PAX6 haploinsufficiency leads to aniridia, whole-gene duplication causes non-aniridic eye malformations, and homozygous loss-of-function is perinatally lethal in humans and mice (Roberts 1967; Glaser et al. 1994; Schedl et al. 1996; Aalfs et al. 1997; Schmidt-Sidor et al. 2009; Schilter et al. 2013).