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ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions

Journal of Human Hypertension volume 30, pages 374–378 (2016)Cite this article

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Abstract

Idiopathic hyperaldosteronism (IHA) due to bilateral adrenal hyperplasia is the most common subtype of primary aldosteronism (PA). The pathogenesis of IHA is still unknown, but the bilateral disease suggests a potential predisposing genetic alteration. Heterozygous germline mutations of armadillo repeat containing 5 (ARMC5) have been shown to be associated with hypercortisolism due to sporadic primary bilateral macronodular adrenal hyperplasia and are also observed in African-American PA patients. We investigated the presence of germline ARMC5 mutations in a group of PA patients who had bilateral computed tomography-detectable adrenal alterations. We sequenced the entire coding region of ARMC5 and all intron/exon boundaries in 39 patients (37 Caucasians and 2 black Africans) with confirmed PA (8 unilateral, 27 bilateral and 4 undetermined subtype) and bilateral adrenal lesions. We identified 11 common variants, 5 rare variants with a minor allele frequency <1% and 2 new variants not previously reported in public databases. We did not detect by in silico analysis any ARMC5 sequence variations that were predicted to alter protein function. In conclusion, ARMC5 mutations are not present in a fairly large series of Caucasian patients with PA associated to bilateral adrenal disease. Further studies are required to definitively clarify the role of ARMC5 in the pathogenesis of adrenal nodules and aldosterone excess in patients with PA.

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Acknowledgements

PM is in receipt of a grant from the Italian Ministry of Instruction, University and Research (Grant ex-60%, 2013) and SM is in receipt of a grant from the Italian Ministry of Instruction, University and Research (Grant ex-60%, 2014). We thank Dr Elisa Taschin and Dr Maria Virginia Lanza (Veneto Institute of Oncology) for technical support in sequencing ARMC5 gene.

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Author notes

  1. P Mulatero, F Schiavi, G Opocher and F Fallo: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Internal Medicine and Hypertension, Department of Medical Sciences–DSM, University of Torino, Torino, Italy

    P Mulatero, T A Williams & S Monticone

  2. Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, University of Padova, Padova, Italy

    F Schiavi, G Barbon & G Opocher

  3. Department of Medicine–DIMED, Clinica Medica 3, University of Padova, Padova, Italy

    F Fallo

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  1. P Mulatero
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Correspondence to P Mulatero.

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Mulatero, P., Schiavi, F., Williams, T. et al. ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions. J Hum Hypertens 30, 374–378 (2016). https://doi.org/10.1038/jhh.2015.98

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