Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism

40 unrelated subjects with hypertension due to primary aldosteronism by age 10, in whom disease-causing mutations in CYP11B2, KCNJ5, and CACNA1D were excluded. An additional 1,632 unrelated subjects (324 with PA diagnosed after age 10, 96 with hypertension and bilateral adrenal hyperplasia, and 1,212 with potential genetic causes of hypertension without PA) and 90 aldosterone-producing adenomas were sequenced for specificity.

Whole-exome sequencing to identify recurrent genetic mutations, followed by in vitro electrophysiological characterization of the identified mutant channel (CACNA1H M1549V) in HEK293T cells.

Identification of recurrent or rare genetic variants causing early-onset primary aldosteronism.surrogate