As an example, the above mentioned ARX P26L variant that disrupts cooperativity, but largely maintains DNA binding affinity, has been associated with epilepsy, whereas ARX P26R disrupts all DNA binding (Barrera et al., 2016; Shoubridge et al., 2012) and has been associated with more severe structural defects such as lissencephaly (Kato et al., 2004). The gene discussed is ARX; the disease is lissencephaly spectrum disorders.