Inherited forms of mineralocorticoid hypertension

Zennaro, Maria-Christina; Boulkroun, Sheerazed; Fernandes-Rosa, Fábio Luiz

doi:10.1016/j.beem.2015.04.010

Cited by 36 publications

(23 citation statements)

References 103 publications

(84 reference statements)

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“…Low renin hypertension may account for up to 30 % of patients with primary "essential" hypertension [32]. It includes a group of monogenic disorders featuring different genetic defects [33] as well as acquired diseases such as in the case of liquorice abuse [32], in which aldosterone levels are low. However, there have been reports suggesting that a subgroup of hypertensive subjects, with normal aldosterone levels, may display some features of abnormal aldosterone regulation, in particular reduced suppression of aldosterone following salt load [34], indicating the possibility of a continuum between low renin hypertension and PA. Aldosterone levels, renin levels and the aldosterone to renin ratio (ARR) correlate with increased blood pressure and increased incidence of hypertension over time in the general population [35][36][37].…”

Section: Genetic Contribution To Aldosterone and Renin Levels And Posmentioning

confidence: 99%

Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond

et al. 2015

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Bilateral adrenal hyperplasia currently accounts for up to 2 thirds of cases of primary aldosteronism. As such, it represents a major opportunity for targeted medical management as opposed to unilateral surgically correctable forms of the disease. Although the majority of cases of primary aldosteronism are sporadic, bilateral adrenal hyperplasia may occur in the context of familial hyperaldosteronism where it is associated with specific germline mutations. Over the past 5 years, impressive progress has been made in our understanding of the genetic basis underlying primary aldosteronism, allowing us to identify and characterize new familial forms of the disease and to understand the mechanisms involved in the formation of aldosterone producing adenoma. In contrast, our knowledge of the genetic contribution to the development of bilateral adrenal hyperplasia, and in a larger context, to renin and aldosterone levels in the general population, is still poor. This review summarizes our current knowledge on the genetics of bilateral adrenal hyperplasia and addresses some open questions to be addressed by future research. In particular, genome-wide association studies in large populations may provide clues to understanding the genetic susceptibility underlying the development of primary aldosteronism.

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Section: Genetic Contribution To Aldosterone and Renin Levels And Posmentioning

confidence: 99%

Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond

et al. 2015

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“…A positive family history increases the overall risk of developing high blood pressure and genetic factors account for 30–50% of the individual risk [ 2 ]. A minority of the hypertensive patients are affected by an inherited disease, resulting from single gene germline mutations affecting mineralocorticoid, glucocorticoid or sympathetic pathways [ 2 , 3 ]. Among these diseases, Liddle syndrome (LS) is caused by point mutations of the epithelial sodium channel (ENaC), that cause renal aldosterone-independent sodium reabsorption.…”

Section: Introductionmentioning

confidence: 99%

Liddle Syndrome: Review of the Literature and Description of a New Case

Tetti

Monticone

Burrello

et al. 2018

IJMS

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Liddle syndrome is an inherited form of low-renin hypertension, transmitted with an autosomal dominant pattern. The molecular basis of Liddle syndrome resides in germline mutations of the SCNN1A, SCNN1B and SCNN1G genes, encoding the α, β, and γ-subunits of the epithelial Na+ channel (ENaC), respectively. To date, 31 different causative mutations have been reported in 72 families from four continents. The majority of the substitutions cause an increased expression of the channel at the distal nephron apical membrane, with subsequent enhanced renal sodium reabsorption. The most common clinical presentation of the disease is early onset hypertension, hypokalemia, metabolic alkalosis, suppressed plasma renin activity and low plasma aldosterone. Consequently, treatment of Liddle syndrome is based on the administration of ENaC blockers, amiloride and triamterene. Herein, we discuss the genetic basis, clinical presentation, diagnosis and treatment of Liddle syndrome. Finally, we report a new case in an Italian family, caused by a SCNN1B p.Pro618Leu substitution.

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“…While the majority of cases of PA are sporadic, 1–5% of cases are familial forms (Zennaro et al, 2015). Familial hyperaldosteronism (FH) type I is a disease with autosomal dominant transmission due to unequal crossing-over of genetic material between the genes coding for aldosterone synthase ( CYP11B2 ) and 11β-hydroxylase ( CYP11B1 ).…”

Section: Introductionmentioning

confidence: 99%

CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism

et al. 2016

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Primary aldosteronism (PA) is the most common form of secondary hypertension. Mutations in KCNJ5, ATP1A1, ATP2B3 and CACNA1D are found in aldosterone producing adenoma (APA) and familial hyperaldosteronism (FH). A recurrent mutation in CACNA1H (coding for Cav3.2) was identified in a familial form of early onset PA. Here we performed whole exome sequencing (WES) in patients with different types of PA to identify new susceptibility genes.Four different heterozygous germline CACNA1H variants were identified. A de novo Cav3.2 p.Met1549Ile variant was found in early onset PA and multiplex developmental disorder. Cav3.2 p.Ser196Leu and p.Pro2083Leu were found in two patients with FH, and p.Val1951Glu was identified in one patient with APA. Electrophysiological analysis of mutant Cav3.2 channels revealed significant changes in the Ca2 + current properties for all mutants, suggesting a gain of function phenotype. Transfections of mutant Cav3.2 in H295R-S2 cells led to increased aldosterone production and/or expression of genes coding for steroidogenic enzymes after K+ stimulation. Identification of CACNA1H mutations associated with early onset PA, FH, and APA suggests that CACNA1H might be a susceptibility gene predisposing to PA with different phenotypic presentations, opening new perspectives for genetic diagnosis and management of patients with PA.

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Inherited forms of mineralocorticoid hypertension

Cited by 36 publications

References 103 publications

Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond

Bilateral Idiopathic Adrenal Hyperplasia: Genetics and Beyond

Liddle Syndrome: Review of the Literature and Description of a New Case

CACNA1H Mutations Are Associated With Different Forms of Primary Aldosteronism

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