title: Discordant genotype-phenotype correlation in familial hyperaldosteronism type III with KCNJ5 gene mutation: a patient report and review of the literature.
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.
  
  
  CONCLUSIONS
  Diverse clinical severity in FH-III cannot be defined solely by KCNJ5 genotype.
authors.affiliation: Department of Endocrinology and Metabolism, Kanagawa Children's Medical Center, Yokohama, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Adachi
authors.forename: Koji
authors.initials: K
authors.lastname: Muroya
authors.forename: Yumi
authors.initials: Y
authors.lastname: Asakura
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Keiko
authors.initials: K
authors.lastname: Homma
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D000311:Adrenal Glands / Q000473:pathology; D019943:Amino Acid Substitution; D002675:Child, Preschool; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage; D020125:Mutation, Missense; D011141:Polyuria / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013148:Spironolactone / Q000008:administration & dosage
chemical_list: D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone