title: Novel genes in primary aldosteronism.
abstract: OBJECTIVE
  Novel high-throughput genetic techniques have increased the pace of discoveries in the field of primary aldosteronism. Mutations in the potassium channel gene KCNJ5 are a cause of familial and sporadic forms of primary aldosteronism with around 30-40% of aldosterone-producing adenomas being affected by somatic mutations.
  
  
  RESULTS
  Exome sequencing of tumors without KCNJ5 mutations revealed genetic alterations in the ATPases ATP1A1 and ATP2B3, with a combined prevalence of 5-7%. Mutations in the gene encoding a subunit of the Ca channel Cav1.3 (CACNA1D) were described with a prevalence of 5-8%. In addition, a new syndrome consisting of primary aldosteronism, seizures, and neuromuscular disease with germline CACNA1D mutations could be identified. All these genetic variants enhance Ca-mediated signalling and steroidogenesis in affected glomerulosa cells and provide the molecular basis for autonomous aldosterone secretion. Furthermore, the pattern of genetic alterations allows for subgrouping of patient cohorts with potentially distinct clinical features including sex and age distribution as well as endocrine and cardiovascular endpoints.
  
  
  CONCLUSIONS
  Altogether in around 50% of aldosterone-producing adenomas, a somatic point mutation can be identified as the underlying genetic cause. These findings will provide the framework for potential identification of new biomarkers and therapeutic targets of this most common form of secondary hypertension.
authors.affiliation: Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Fischer
authors.forename: Felix
authors.initials: F
authors.lastname: Beuschlein
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000235:genetics*; D018246:Adrenocortical Adenoma / Q000235:genetics*; D000450:Aldosterone / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D006929:Hyperaldosteronism / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
chemical_list: D020746:Calcium Channels, L-Type; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000450:Aldosterone; C499076:ATP1A1 protein, human; D000254:Sodium-Potassium-Exchanging ATPase