Whole-exome sequencing has shown that loss-of-function mutations in the human EPHB4 gene cause a rare disease termed Capillary Malformation-Arteriovenous Malformation (CM-AVM2)36,108, characterized by cutaneous capillary malformations and AV defects such as arteriovenous fistulas. Here, EPHB4 is linked to cutaneous mastocytosis.