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Novel genes in primary aldosteronism

Fischer, Evelyn; Beuschlein, Felix

Current Opinion in Endocrinology, Diabetes and Obesity: June 2014 - Volume 21 - Issue 3 - p 154–158
doi: 10.1097/MED.0000000000000060

Purpose of review Novel high-throughput genetic techniques have increased the pace of discoveries in the field of primary aldosteronism. Mutations in the potassium channel gene KCNJ5 are a cause of familial and sporadic forms of primary aldosteronism with around 30–40% of aldosterone-producing adenomas being affected by somatic mutations.

Recent findings Exome sequencing of tumors without KCNJ5 mutations revealed genetic alterations in the ATPases ATP1A1 and ATP2B3, with a combined prevalence of 5–7%. Mutations in the gene encoding a subunit of the Ca2+ channel Cav1.3 (CACNA1D) were described with a prevalence of 5–8%. In addition, a new syndrome consisting of primary aldosteronism, seizures, and neuromuscular disease with germline CACNA1D mutations could be identified. All these genetic variants enhance Ca2+-mediated signalling and steroidogenesis in affected glomerulosa cells and provide the molecular basis for autonomous aldosterone secretion. Furthermore, the pattern of genetic alterations allows for subgrouping of patient cohorts with potentially distinct clinical features including sex and age distribution as well as endocrine and cardiovascular endpoints.

Summary Altogether in around 50% of aldosterone-producing adenomas, a somatic point mutation can be identified as the underlying genetic cause. These findings will provide the framework for potential identification of new biomarkers and therapeutic targets of this most common form of secondary hypertension.

Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany

Correspondence to Professor Dr med. Felix Beuschlein, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ziemssenstr. 1, 80336 Munich, Germany. Tel: +49 89 5160 2110; fax: +49 89 5160 4467; e-mail:

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins