SIX3 and holoprosencephaly: Recently, Fgf8 was included among major genes implicated in holoprosencephaly due to its frequency of mutation (2.3%) in a cohort of 257 diagnosed patients, similar to the frequencies of Six3 (2.7%) and Gli2 (3.1%), two other holoprosencephaly-related genes (see above; Dubourg et al., 2016).