Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: A patient report and review of the literature

Masanori Adachi, Koji Muroya, Yumi Asakura, Kenji Sugiyama, Keiko Homma, Tomonobu Hasegawa

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: Familial hyperaldosteronism type III (FH-III) is a rare autosomal dominant disease for which five missense mutations in KCNJ5 have been identified. FH-III has a wide phenotypic variability from spironolactone-responsive hyperaldosteronism to massive adrenal hypertrophy with drug-resistant hypertension. This variation has mainly been attributed to genotype, because, in contrast to other genotypes (G151R, T158A, I157S, and Y152C), (1) FH-III patients with G151E have shown milder phenotype, and (2) G151E-harboring cells were found to have rapid lethality due to much larger sodium conductance of the encoded channel (Kir3.4), which prevents adrenal hypertrophy. Methods: Here we describe the clinical course of a sporadic case of FH-III, with de novo G151R mutation. Results: The patient developed polyuria at around 1.5 years of age and developed hypertension and hypokalemia by 4 years of age. Thereafter, spironolactone treatment successfully ameliorated hyperaldosteronism for 7 years with no discernible adrenal enlargement. Conclusion: Diverse clinical severity in FH-III cannot be defined solely by KCNJ5 genotype.

Original languageEnglish
Pages (from-to)138-142
Number of pages5
JournalHormone Research in Paediatrics
Volume82
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Endocrine hypertension
  • Familial hyperaldosteronism
  • KCNJ5
  • Kir3.4
  • Primary aldosteronism

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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