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ARMC5 is not implicated in familial hyperaldosteronism type II (FH-II)

Journal of Human Hypertension volume 31, pages 857–859 (2017)Cite this article

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Germline loss-of-function mutations in the armadillo-repeat-containing 5 ( ARMC5) gene are an established cause of Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia (BMAH), 1, 2 and may play a role in primary aldosteronism. 3 As familial hyperaldosteronism type II (FH-II) has a presumed genetic basis, 4 we hypothesised that germline ARMC5 mutations underlie FH-II. We interrogated whole-exome sequencing data from four FH-II families. We did not identify any pathogenic ARMC5 variants which segregated with the phenotype of primary aldosteronism.

Accounting for up to 6% of primary aldosteronism,5 FH-II is a familial form of aldosterone excess which is otherwise clinically indistinguishable from sporadic primary aldosteronism and not glucocorticoid remediable.6 Expression is variable, even within families, manifesting as unilateral or bilateral hyperaldosteronism due to adrenal adenomas or hyperplasia.6 Inheritance appears to be autosomal dominant with incomplete penetrance.5 Studies of plausibly related genes such as AT1 (angiotensin II type 1 receptor), CYP11B2 (aldosterone synthase) and MEN1 have been negative.7 Multipoint linkage analysis of a large FH-II kindred suggested a locus at 7p22 (LOD score 3.26),8 which has since been refined although studies of regional genes have been unrevealing.9 Whilst the genetic cause of FH-II remains elusive, the genetic basis of rarer familial forms of primary aldosteronism has been elucidated with FH-I due to CYP11B1/CYP11B2 fusion, FH-III due to KCNJ5 mutations, and FH-IV due to CACNA1H mutations.10

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Acknowledgements

SMCS is supported by a Royal Adelaide Hospital A.R. Clarkson Scholarship.

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Authors and Affiliations

  1. Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, Australia

    S M C De Sousa, D J Torpy & L Gagliardi

  2. School of Medicine, University of Adelaide, Adelaide, Australia

    S M C De Sousa, C N Hahn, D J Torpy, H S Scott & L Gagliardi

  3. Department of Genetics and Molecular Pathology, Centre for Cancer Biology, an SA Pathology and University of South Australia alliance, Adelaide, Australia

    S M C De Sousa, C N Hahn, H S Scott & L Gagliardi

  4. Endocrine Hypertension Research Centre, University of Queensland School of Medicine, Greenslopes and Princess Alexandria Hospitals, Brisbane, Australia

    M Stowasser & R D Gordon

  5. ACRF Cancer Genomics Facility, Centre for Cancer Biology, SA Pathology, Adelaide, Australia

    J Feng, A W Schreiber, P Wang & H S Scott

  6. School of Biological Sciences, University of Adelaide, Adelaide, Australia

    A W Schreiber & H S Scott

  7. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia

    H S Scott

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  1. S M C De Sousa
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  8. D J Torpy
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Correspondence to S M C De Sousa.

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De Sousa, S., Stowasser, M., Feng, J. et al. ARMC5 is not implicated in familial hyperaldosteronism type II (FH-II). J Hum Hypertens 31, 857–859 (2017). https://doi.org/10.1038/jhh.2017.71

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