Skip Navigation LinksHome > June 2014 - Volume 21 - Issue 3 > Novel genes in primary aldosteronism
Current Opinion in Endocrinology, Diabetes & Obesity:
doi: 10.1097/MED.0000000000000060
ADRENAL CORTEX AND MEDULLA: Edited by Anand Vaidya

Novel genes in primary aldosteronism

Fischer, Evelyn; Beuschlein, Felix

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Abstract

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.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

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