Defects in KCNJ16 Cause a Novel Tubulopathy with Hypokalemia, Salt Wasting, Disturbed Acid-Base Homeostasis, and Sensorineural Deafness.

Acid-Base Imbalance / genetics Adolescent Adult Alleles Animals Child, Preschool Female Hearing Loss, Sensorineural / genetics Humans Hypokalemia / genetics Infant Infant, Newborn Kidney Diseases / genetics Kidney Tubules Loss of Function Mutation Male Mice Nephrons / metabolism Oocytes Pedigree Phenotype Potassium Channels, Inwardly Rectifying / genetics RNA, Messenger / metabolism Renal Reabsorption / genetics Salts / metabolism Exome Sequencing Xenopus laevis Young Adult

KCNJ10 KCNJ15 KCNJ16 acid-base homeostasis deafness distal tubule hypokalemia potassium channels proximal tubule tubulopathy

Journal

Journal of the American Society of Nephrology : JASN

ISSN: 1533-3450

Titre abrégé: J Am Soc Nephrol

Pays: United States

ID NLM: 9013836

Informations de publication

Date de publication:
01 06 2021

Historique:

received: 11 11 2020

accepted: 04 02 2021

pubmed: 4 4 2021

medline: 5 10 2021

entrez: 3 4 2021

Statut: ppublish

Résumé

The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants. We identified mutations in the Biallelic variants in

Sections du résumé

BACKGROUND

METHODS

A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants.

RESULTS

We identified mutations in the

CONCLUSIONS

Biallelic variants in

Identifiants

DOI: 10.1681/ASN.2020111587 PMID: 33811157 PMC: PMC8259640

pubmed: 33811157

pii: 00001751-202106000-00023

doi: 10.1681/ASN.2020111587

pmc: PMC8259640

doi:

Substances chimiques

KCNJ16 protein, human 0

Kcnj10 (channel) 0

Kcnj16 protein, mouse 0

Kir4.2 channel 0

Potassium Channels, Inwardly Rectifying 0

RNA, Messenger 0

Salts 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

Pagination

1498-1512

Subventions

Organisme : BLRD VA

ID : I01 BX004024

Pays : United States

Organisme : NHLBI NIH HHS

ID : R35 HL135749

Pays : United States

Informations de copyright

Références

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