{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:38:36Z","timestamp":1791923916547,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T00:00:00Z","timestamp":1654732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Somatic mutations for excess aldosterone production have been frequently identified as important roles in the pathogenesis of unilateral primary hyperaldosteronism (uPA). Although <jats:italic>CACNA1H<\/jats:italic> mutation represents a minor etiology in primary aldosteronism, it plays a significant role in causing uPAs in sporadic cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To identify novel somatic <jats:italic>CACNA1H<\/jats:italic> mutation in patients with uPA and investigate the pathophysiological, immunohistological, and clinical characteristics of the variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We applied a customized and targeted gene panel next-generation sequencing approach to detect mutations from the uPA cohort in Taiwan Primary Aldosteronism Investigation study group. Information from pre-diagnostic to postoperative data was collected, including past history, medications, blood pressure readings, biochemical data, and image studies. The functional role of the variant was confirmed by <jats:italic>in vitro<\/jats:italic> studies, demonstrating aldosterone production in variant-transfected human adrenal cell lines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified a novel somatic <jats:italic>CACNA1H<\/jats:italic> mutation c.5809G&amp;gt;A (p.Val1937Met) in a uPA case. The <jats:italic>CACNA1H<\/jats:italic> gene encodes the pore-forming alpha-1H subunit of the voltage-dependent T-type calcium channel Cav3.2. This somatic <jats:italic>CACNA1H<\/jats:italic> p.V1937M variant showed excellent clinical and biochemical outcomes after ipsilateral adrenalectomy. The functional effect of somatic <jats:italic>CACNA1H<\/jats:italic> p.V1937M variant results in increased CYP11B2 expression and aldosterone biosynthesis in HAC15 cells. A distinct heterogeneous foamy pattern of CYP11B2 and CYP17A1 expression was identified in immunohistological staining, supporting the pathological evidence of aldosterone synthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The somatic mutation of <jats:italic>CACNA1H<\/jats:italic> p.V1937M might be a pathogenic driver in aldosterone overproduction. This study provides new insight into the molecular mechanism and disease outcomes of uPA.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.816476","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T04:53:41Z","timestamp":1654750421000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["A Novel Somatic Mutation of CACNA1H p.V1937M in Unilateral Primary 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