Somatic CACNA1H Mutation As a Cause of Aldosterone-Producing Adenoma

Research output: Contribution to journalArticle

Authors

  • Kazutaka Nanba
  • Amy R. Blinder
  • Juilee Rege
  • Namita G. Hattangady
  • Tobias Else
  • Chia Jen Liu
  • Scott A. Tomlins
  • Pankaj Vats
  • Chandan Kumar-Sinha
  • Thomas J. Giordano
  • William E. Rainey

External Institution(s)

  • University of Michigan, Ann Arbor

Details

Original languageEnglish (US)
Pages (from-to)645-649
Number of pages5
JournalHypertension
StatusPublished - Mar 1 2020
Peer-reviewedYes

Abstract

Driver somatic mutations for aldosterone excess have been found in ≈90% of aldosterone-producing adenomas (APAs) using an aldosterone synthase (CYP11B2)-guided sequencing approach. In the present study, we identified a novel somatic CACNA1H mutation (c.T4289C, p.I1430T) in an APA without any currently known aldosterone-driver mutations using CYP11B2 immunohistochemistry-guided whole exome sequencing. The CACNA1H gene encodes a voltage-dependent T-type calcium channel alpha-1H subunit. Germline variants in this gene are known as a cause of familial hyperaldosteronism IV. Targeted next-generation sequencing detected identical CACNA1H variants in 2 additional APAs in a cohort of the University of Michigan, resulting in a prevalence of 4% (3/75) in APAs. We tested the functional effect of the variant on adrenal cell aldosterone production and CYP11B2 mRNA expression using the human adrenocortical HAC15 cell line with a doxycycline-inducible CACNA1HI1430T mutation. Doxycycline treatment increased CYP11B2 mRNA levels as well as aldosterone production, supporting a pathological role of the CACNA1H p.I1430T mutation on the development of primary aldosteronism. In conclusion, somatic CACNA1H mutation is a genetic cause of APAs. Although the prevalence of this mutation is low, this study will provide better understanding of molecular mechanism of inappropriate aldosterone production in APAs.

    Research areas

  • Aldosterone, Aldosterone-producing adenoma, CYP11B2, Calcium channel, Mutation, Primary aldosteronism

Citation formats

APA

Nanba, K., Blinder, A. R., Rege, J., Hattangady, N. G., Else, T., Liu, C. J., ... Rainey, W. E. (2020). Somatic CACNA1H Mutation As a Cause of Aldosterone-Producing Adenoma. Hypertension, 645-649. https://doi.org/10.1161/HYPERTENSIONAHA.119.14349

Harvard

Nanba, K, Blinder, AR, Rege, J, Hattangady, NG, Else, T, Liu, CJ, Tomlins, SA, Vats, P, Kumar-Sinha, C, Giordano, TJ & Rainey, WE 2020, 'Somatic CACNA1H Mutation As a Cause of Aldosterone-Producing Adenoma', Hypertension, pp. 645-649. https://doi.org/10.1161/HYPERTENSIONAHA.119.14349