title: ARMC5 mutation analysis in patients with primary aldosteronism and bilateral adrenal lesions.
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.
authors.affiliation: Division of Internal Medicine and Hypertension, Department of Medical Sciences-DSM, University of Torino, Torino Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mulatero
authors.affiliation: Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, University of Padova, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Schiavi
authors.affiliation: Division of Internal Medicine and Hypertension, Department of Medical Sciences-DSM, University of Torino, Torino Italy.
authors.forename: T A
authors.initials: TA
authors.lastname: Williams
authors.affiliation: Division of Internal Medicine and Hypertension, Department of Medical Sciences-DSM, University of Torino, Torino Italy.
authors.forename: S
authors.initials: S
authors.lastname: Monticone
authors.affiliation: Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Barbon
authors.affiliation: Familial Cancer Clinic and Oncoendocrinology, Veneto Institute of Oncology, IRCCS, University of Padova, Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Opocher
authors.affiliation: Department of Medicine-DIMED, Clinica Medica 3, University of Padova, Padova, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Fallo
mesh_terms: D000312:Adrenal Hyperplasia, Congenital / Q000000981:diagnostic imaging / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D051186:Armadillo Domain Proteins; D044383:Black People / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D006929:Hyperaldosteronism / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D007558:Italy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: C000590373:ARMC5 protein, human; D051186:Armadillo Domain Proteins; D025521:Tumor Suppressor Proteins