Crucially, for many of these TFs, disruption of positive feedback has been identified as the cause of human disease, including LMX1B in nail–patella syndrome (Haro et al., 2021), PAX6 in aniridia (Bhatia et al., 2013), SOX10 in Waardenburg syndrome (Lecerf et al., 2014), SOX9 in sex reversal (Croft et al., 2018), FOXG1 in FOXG1 syndrome (Ye et al., 2022), FOXP2 in speech–language disorder (Becker et al., 2018), NFIA in a brain malformation syndrome (Trevino et al., 2021), GATA2 in immunodeficiency (Johnson et al., 2012), and HNF1A and HNF4A in MODY (Hansen et al., 2002). Here, SOX9 is linked to immunodeficiency disease.