Spontaneous independent de novo p.Tyr129Phe mutations were shown to cause dominant mandibulofacial dysostosis with alopecia in humans and a recombinant EDNRA with the Tyr129Phe mutation is no longer able to activate downstream signaling upon stimulation with either EDN1 or EDN3 (OMIM 616367)32. The gene discussed is EDN1; the disease is mandibulofacial dysostosis.