The difference between both abnormalities lies in the structure of the chromatin domains: in the case of limb malformation (Cooks syndrome, OMIM #106995), a new chromatin domain is formed that insulates the duplication from SOX9 (Figure 4), whereas in sex reversal (OMIM #278850) the duplication resides within the SOX9 TAD and therefore affects its expression. Here, SOX9 is linked to Cooks syndrome.