While CS mice exhibit a clear increase in severity of both cardiovascular and GI pathology that correlates with the severity of the molecular defect (from SUR2[A478V] to Kir6.1[V65M] and from hetero- to homozygous presentation), GI problems in human CS are quite variable, and at this juncture, we cannot discern a clear molecular mutation disease severity correlation. Here, KCNJ8 is linked to Cowden syndrome 1.