Biallelic loss-of-function variants in KCNJ16 presenting with hypokalemic metabolic acidosis

Eur J Hum Genet. 2021 Oct;29(10):1566-1569. doi: 10.1038/s41431-021-00883-0. Epub 2021 Apr 12.

Abstract

KCNJ16 encodes Kir5.1 and acts in combination with Kir4.1, encoded by KCNJ10, to form an inwardly rectifying K+ channel expressed at the basolateral membrane of epithelial cells in the distal nephron. This Kir4.1/Kir5.1 channel is critical for controlling basolateral membrane potential and K+ recycling, the latter coupled to Na-K-ATPase activity, which determines renal Na+ handling. Previous work has shown that Kcnj16-/- mice and SSKcnj16-/- rats demonstrate hypokalemic, hyperchloremic metabolic acidosis. Here, we present the first report of a patient identified to have biallelic loss-of-function variants in KCNJ16 by whole exome sequencing who presented with chronic metabolic acidosis with exacerbations triggered by minor infections.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis / genetics*
  • Acidosis / pathology
  • Alleles
  • Child, Preschool
  • Female
  • Humans
  • Hypokalemia / genetics*
  • Hypokalemia / pathology
  • Loss of Function Mutation*
  • Potassium Channels, Inwardly Rectifying / genetics*

Substances

  • KCNJ16 protein, human
  • Potassium Channels, Inwardly Rectifying