Activating mutations in ABCC9 cause Cantú syndrome

Cantú syndrome is characterized by congenital hypertrichosis, characteristic facial abnormalities, cardiomegaly and osteochondrodyplasia. We use family based exome sequencing and identified a de novo mutation in ABCC9 and subsequently identified dominant missense mutations in ABCC9 in 14 out of 16 cases. ABCC9 is part of an ATP dependent potassium channel; we show that mutations in ABCC9 reduce the ATP-mediated inhibition of this channel. Our findings may have direct implications for the treatment of Cantú patients because ABCC9 is a known pharmaceutical target.