TY - JOUR
T1 - Biallelic loss-of-function variants in KCNJ16 presenting with hypokalemic metabolic acidosis
AU - Webb, Bryn D.
AU - Hotchkiss, Hilary
AU - Prasun, Pankaj
AU - Gelb, Bruce D.
AU - Satlin, Lisa
N1 - Funding Information:
Funding This work is supported by the Mindich Child Health and Development Institute (MCHDI) at the Icahn School of Medicine at Mount Sinai and the Genetic Disease Foundation (New York, NY). BDW receives support from National Institutes of Health National Institute of Child Health and Development (K08HD086827).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to European Society of Human Genetics.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85104123558&partnerID=8YFLogxK
U2 - 10.1038/s41431-021-00883-0
DO - 10.1038/s41431-021-00883-0
M3 - Article
C2 - 33840812
AN - SCOPUS:85104123558
SN - 1018-4813
VL - 29
SP - 1566
EP - 1569
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 10
ER -