Document Detail

New insights into aldosterone-producing adenomas and hereditary aldosteronism: mutations in the K+ channel KCNJ5.
MedLine Citation:
PMID:  23318698     Owner:  NLM     Status:  MEDLINE    
PURPOSE OF REVIEW: Primary aldosteronism is a major cause of secondary hypertension worldwide. This review describes the recent studies that have provided dramatic new insight into the pathogenesis of aldosterone-producing adenomas (APAs) and inherited primary aldosteronism, revealing the role of mutations in the potassium channel KCNJ5 in these disorders.
RECENT FINDINGS: Either of two somatic gain-of-function mutations in the inward rectifier potassium channel KCNJ5 (Kir3.4) are present in approximately 40% of APAs. These tumor-causing mutations are heterozygous and alter the channel's selectivity filter. Mutant channels gain permeability to sodium, resulting in cellular depolarization and activation of voltage-gated calcium channels. The resulting calcium influx is sufficient to produce aldosterone secretion and cell proliferation, accounting for APA development. Germline KCNJ5 mutations also result in either of two autosomal-dominant syndromes featuring early-onset primary aldosteronism. Mutations identical or similar to those found in APAs result in massive bilateral adrenal hyperplasia. A different mutation at the same position produces a less severe syndrome without adrenal hyperplasia because this mutation results in Na-dependent cell lethality caused by a drastic increase in Na conductance.
SUMMARY: These findings provide fundamental insight into the pathogenesis of APAs and primary aldosteronism, and have implications for new diagnostic and therapeutic strategies.
Ute I Scholl; Richard P Lifton
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current opinion in nephrology and hypertension     Volume:  22     ISSN:  1473-6543     ISO Abbreviation:  Curr. Opin. Nephrol. Hypertens.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-07-26     Revised Date:  2013-08-29    
Medline Journal Info:
Nlm Unique ID:  9303753     Medline TA:  Curr Opin Nephrol Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  141-7     Citation Subset:  IM    
Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA.
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MeSH Terms
Adrenal Cortex Neoplasms / genetics*,  metabolism,  pathology
Adrenocortical Adenoma / genetics*,  metabolism,  pathology
Calcium / metabolism
Calcium Channels / metabolism
G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*,  metabolism
Genetic Predisposition to Disease
Hyperaldosteronism / genetics*,  metabolism,  pathology
Ion Channel Gating
Potassium / metabolism
Sodium / metabolism
Grant Support
//Howard Hughes Medical Institute
Reg. No./Substance:
0/Calcium Channels; 0/G Protein-Coupled Inwardly-Rectifying Potassium Channels; 0/KCNJ5 protein, human; 7440-09-7/Potassium; 7440-23-5/Sodium; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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