Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas

Azizan Elena Aisha, Meena Murthy, Michael Stowasser, Richard Gordon, Bartosz Kowalski, Shengxin Xu, Morris J. Brown, Kevin M. O'Shaughnessy

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Primary hyperaldosteronism, one cause of which is aldosterone-producing adenomas (APAs), may account for ≤5% to 10% of cases of essential hypertension. Germline mutations have been identified in 2 rare familial forms of primary hyperaldosteronism, but it has been reported recently that somatic mutations of the KCNJ5 gene, which encodes a potassium channel, are present in some sporadic nonsyndromic APAs. To address this further we screened 2 large collections of sporadic APAs from the United Kingdom and Australia (totalling 73) and found somatic mutations in the selectivity filter of KCNJ5 in 41% (95% CI: 31% to 53%) of the APAs (30 of 73). These included the previously noted nonsynonymous mutations, G151R and L158R, and an unreported 3-base deletion, delI157, in the region of the selectivity filter. APAs containing a somatic KCNJ5 mutation were significantly larger than those without (1.61 cm [95% CI: 1.39-1.83 cm] versus 1.04 cm [95% CI: 0.91-1.17 cm]; P2 cm), and their frequency in our unselected series suggests they are common and could be important in the molecular pathogenesis of many sporadic cases of APA.

Original languageEnglish
Pages (from-to)587-591
Number of pages5
JournalHypertension
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2012
Externally publishedYes

Fingerprint

Aldosterone
Adenoma
Mutation
Hyperaldosteronism
Germ-Line Mutation
Potassium Channels
Genes

Keywords

  • aldosterone-producing adenoma
  • hyperaldosteronism
  • hypertension
  • KCNJ5
  • posture response
  • potassium channels

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. / Elena Aisha, Azizan; Murthy, Meena; Stowasser, Michael; Gordon, Richard; Kowalski, Bartosz; Xu, Shengxin; Brown, Morris J.; O'Shaughnessy, Kevin M.

In: Hypertension, Vol. 59, No. 3, 03.2012, p. 587-591.

Research output: Contribution to journalArticle

Elena Aisha, Azizan ; Murthy, Meena ; Stowasser, Michael ; Gordon, Richard ; Kowalski, Bartosz ; Xu, Shengxin ; Brown, Morris J. ; O'Shaughnessy, Kevin M. / Somatic mutations affecting the selectivity filter of KCNJ5 are frequent in 2 large unselected collections of adrenal aldosteronomas. In: Hypertension. 2012 ; Vol. 59, No. 3. pp. 587-591.
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