It is well-known that Ptch gain-of-function can cause HPE due to ventralization of the neural tube and incorrect specification of the forebrain (Goodrich et al., 1999; Mullor and Guerrero, 2000), however, it has yet to be determined whether rescuing DNA damage can ameliorate the effect of Shh over-activation in this case. The gene discussed is SHH; the disease is holoprosencephaly.