UNIGE document Scientific Article - Letter
previous document  unige:32239  next document
add to browser collection

KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron

CollaborationWith : Ehret, Georg Benedikt
Published in Nature genetics. 2012, vol. 44, no. 4, p. 456-60,S1-3
Abstract Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure.
Keywords AdolescentAdultAgedAged, 80 and overAmino Acid SequenceBase SequenceBlood Pressure/geneticsCarrier Proteins/geneticsChildFemaleHumansIon Transport/geneticsKidney/metabolismMaleMiddle AgedMolecular Sequence DataNephrons/metabolismPolymorphism, Single NucleotidePseudohypoaldosteronism/genetics/metabolism/physiopathologySequence Analysis, DNASignal TransductionSodium Chloride Symporters/genetics/metabolismYoung Adult
PMID: 22406640
Full text
Article (Published version) (1.4 MB) - document accessible for UNIGE members only Limited access to UNIGE
Research group Traits génétiques complexes (901)
(ISO format)
COLLABORATION. KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron. In: Nature Genetics, 2012, vol. 44, n° 4, p. 456-60,S1-3. doi: 10.1038/ng.2218 https://archive-ouverte.unige.ch/unige:32239

453 hits



Deposited on : 2013-12-17

Export document
Format :
Citation style :