CED is caused by mutations in the TGF-β1 gene, resulting in premature activation of TGF-β1.392–395 Approximately 11 different TGF-β1 mutations have been identified from CED-afflicted families.396,397 All mutations are in the region encoding LAP, which either destabilize disulfide bridging of LAP or affect secretion of the protein, leading to enhanced TGF-β1 signaling. This evidence concerns the gene TGFB2 and cranioectodermal dysplasia.