Rare germline variants in canonical and candidate genes in apparently sporadic bilateral primary aldosteronism.

Authors

Lucas S Santana, Débora K Alves-Fernandes, Jose Antonio B Lima Sobrinho, Felipe Freitas-Castro, Lucas B Rossetti, Jessica Okubo, Gustavo F C Fagundes, Eduardo Z Kawahara, Thiago S Mendes, Luiz A Bortolotto, Andrea Pio-Abreu, Giovanio V Silva, Luciano F Drager, Ana Claudia Latronico, Madson Q Almeida

Published in

Journal of the Endocrine Society. Volume 10. Issue 9. Pages bvag167. Epub Jul 27, 2026.

Abstract

The germline genetic basis of bilateral primary aldosteronism (PA) remains poorly understood, particularly in apparently sporadic disease. We investigated rare germline variants in canonical and candidate genes in patients with bilateral PA associated with resistant hypertension and/or hypertension diagnosed before 40 years of age.
We studied 53 individuals with bilateral PA after exclusion of familial PA types 1 and 3. Whole-exome sequencing was performed in 52 probands and 1 affected relative. Variant prioritization was restricted to genes with direct or indirect evidence linking them to PA using a virtual panel approach. Clinical, biochemical, and imaging data were compared between carriers and noncarriers.
Nine of 53 patients (17%) harbored at least one rare germline candidate variant. Variants in canonical PA genes were identified in 5 patients (9.6%), including CACNA1H (n = 4) and CACNA1D (n = 1). In 4 patients (7.5%), rare variants were identified in plausible candidate genes (ANO1, KCNK3, CASZ1, and STRN). All prioritized variants were classified as variants of uncertain significance. Compared with noncarriers, carriers showed a lower frequency of hypokalemia (P < .0001), higher prevalence of family history of hypertension (P < .0001), higher frequency of resistant hypertension (P < .0001), required more antihypertensives (P = .0264), and had more frequent adrenal computed tomography abnormalities, particularly bilateral involvement (P < .0001).
Rare germline variants in canonical and candidate genes were identified in a subset of patients with apparently sporadic bilateral PA. Variants in established genes, particularly CACNA1H, were relatively frequent, with additional variants in biologically plausible candidates.

PMID:
42577001
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.