Rapid characterization of the functional and pharmacological consequences of Cantu syndrome KATP channel mutations in intact cells

Abstract

Gain-of-function (GOF) of vascular KATP channels, resulting from mutations in either KCNJ8 (encoding Kir6.1) or ABCC9 (encoding SUR2) cause Cantu Syndrome (CS), a channelopathy characterized by excess hair growth, coarse facial appearance, cardiomegaly, and lymphedema. Understanding mutation consequences for channel function can help with disease diagnosis and personalized treatment. Here, we established a pipeline for rapid analysis of CS mutations. Stable HEK cell lines were generated expressing human Kir6.1 and SUR2B with previously published (V65M, C176S, E189K in Kir6.1 and A478V, R1150Q, R1150W in SUR2B) or novel (A46V and D338E in Kir6.1 and I419T, indel in SUR2B) CS-associated mutations.