Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1

Chang, Sue S.; Gründer, Stefan; Hanukoglu, Aaron; Rösler, Ariel; Mathew, P. M.; Hanukoglu, Israel; Schild, Laurent; Lu, Yin; Shimkets, Richard A.; Nelson‐Williams, Carol; Rossier, Bernard C.; Lifton, Richard P.

doi:10.1038/ng0396-248

Cited by 737 publications

(453 citation statements)

References 34 publications

Supporting

Mentioning

439

Contrasting

Unclassified

Order By: Relevance

“…They are caused by a large number of now known inactivating mutations affecting all three subunits of ENaC channels (Figs. 5 and 10; Chang et al 1996;Strautnieks et al 1996). ENaCs-as described above-translate the aldosterone signal into an increased Na + reabsorption, which is prevented by the lossof-function mutations causing salt wasting and hypotension.…”

Section: Monogenic Hypotensionmentioning

confidence: 98%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

View full text Add to dashboard Cite

Human hypertension affects affects more than 20% of the adult population in industrialized countries, and it is implicated in millions of deaths worldwide each year from stroke, heart failure and ischemic heart disease. Available evidence suggests a major genetic impact on blood pressure regulation. Studies in monogenic hypertension revealed that renal salt and volume regulation systems are predominantly involved in the genesis of these disorders. Mutations here affect the synthesis of mineralocorticoids, the function of the mineralocorticoid receptor, epithelial sodium channels and their regulation by a new class of kinases, termed WNK kinases. It has been learned from monogenic hypotension that almost all ion transporters involved in the renal uptake of Na + have a major impact on blood pressure regulation. For essential hypertension as a complex disease, many candidate genes have been analysed. These include components of the reninangiotensin-aldosterone system, adducin, β-adrenoceptors, G protein subunits, regulators of G protein signalling (RGS) proteins, Rho kinases and G protein receptor kinases. At present, the individual impact of common polymorphisms in these genes on the observed blood pressure variation, on risk for stroke and as predictors of antihypertensive responses remains small and clinically irrelevant. Nevertheless, these studies have greatly augmented our knowledge on the regulation of renal functions, cellular signal transduction and the integration of both. Together, this provides the basis for the identification of novel drug targets and, hopefully, innovative antihypertensive drugs.

show abstract

Section: Monogenic Hypotensionmentioning

confidence: 98%

Genetics of arterial hypertension and hypotension

Rosskopf

Schürks

Rimmbach

et al. 2007

Naunyn-Schmied Arch Pharmacol

View full text Add to dashboard Cite

show abstract

“…Although autosomal dominant PHA type 1 has been linked to mutations in the mineralocorticoid receptor-coding gene NR3C2, mutations in the ENaC subunit genes (SCNN1A, SCNN1B and SCNN1G) cause the more severe phenotype of autosomal recessive PHA type 1. 5 Autosomal recessive PHA1 is a life-long disease, and patients with inactivating SCNN1A, SCNN1B or SCNN1G mutations show no improvement over time, being prone to life-threatening salt-losing crises combined with severe hyperkalemia and dehydration.…”

Section: Casementioning

confidence: 99%

Unimpaired postnatal respiratory adaptation in a preterm human infant with a homozygous ENaC-α unit loss-of-function mutation

et al. 2011

View full text Add to dashboard Cite

“…Loss-of-function mutations in one of the Na + -channel subunits cause the neonatal salt-wasting disorder pseudohypoaldosteronism type I [9]. Targeted disruption of the β or γ subunits in mice produces a similar phenotype [10,11].…”

Section: Introductionmentioning

confidence: 99%