GLI2 and holoprosencephaly: First, although single-allele GLI2 mutations have been detected in individuals with HPE-like phenotypes, the majority of mutation carriers do not exhibit the full manifestation of HPE or are clinically unaffected (Bear et al., 2014; Franca et al., 2010; Roessler et al., 2003; Bertolacini et al., 2012; Rahimov et al., 2006).