Identification of Somatic Mutations in in Aldosterone-Producing Adenomas.

Somatic mutations driving aldosterone production have been identified in approximately 90% of aldosterone-producing adenomas (APAs) using an aldosterone synthase (CYP11B2) immunohistochemistry (IHC)-guided DNA sequencing approach. In the present study, using CYP11B2-guided whole-exome sequencing (WES) and targeted amplicon sequencing, we detected 2 somatic variants in in 2 APAs that were negative for currently known aldosterone-driver mutations. The gene encodes the voltage-gated chloride channel ClC-2. germline variants have previously been shown to cause familial hyperaldosteronism type II. Somatic mutations in were identified in 2 of 115 APAs, resulting in a prevalence of 1.74%. One of the somatic mutations (c.G71A,p.G24D) was identical to a previously described germline variant causing early-onset PA, but was present only as a somatic mutation. The second mutation, which affects the same region of the gene, has not been reported previously (c.64-2_74del). These findings prove that WES of CYP11B2-guided mutation-negative APAs can help determine rarer genetic causes of sporadic PA.