Renin–aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes

Hanukoglu, Aaron; Edelheit, Oded; Shriki, Yafit; Giżewska, Maria; Dascal, Nathan; Hanukoglu, Israel

doi:10.1016/j.jsbmb.2008.06.013

Cited by 57 publications

(58 citation statements)

References 29 publications

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“…A possible explanation for the lower frequency of complications found in the 'no mutation' group compared with the other groups could be related either to genetic background or more probably to less severe potassium and salt wasting, which induces less activation of the renin-aldosterone axis and fewer deleterious consequences on the GH-IGF1 axis and the metabolic pathways (18,34,35).…”

Section: Discussionmentioning

confidence: 93%

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Balavoine

Bataille

Vanhille

et al. 2011

European Journal of Endocrinology

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Introduction: Gitelman syndrome (GS) is a tubulopathy caused by SLC12A3 gene mutations, which lead to hypokalaemic alkalosis, secondary hyperaldosteronism, hypomagnesaemia and hypocalciuria. Aim: The aim of this study was to assess the prevalence of SLC12A3 gene mutations in adult hypokalaemic patients; to compare the phenotype of homozygous, heterozygous and non-mutated patients; and to determine the efficiency of treatment. Methods: Clinical, biological and genetic data were recorded in 26 patients. Results: Screening for the SLC12A3 gene detected two mutations in 15 patients (six homozygous and nine compound heterozygous), one mutation in six patients and no mutation in five patients. There was no statistical difference in clinical symptoms at diagnosis between the three groups. Systolic blood pressure tended to be lower in patients with two mutations (PZ0.16). Hypertension was unexpectedly detected in four patients. Five patients with two mutated alleles and two with heterozygosity had severe manifestations of GS. Significant differences were observed between the three groups in blood potassium, chloride, magnesium, supine aldosterone, 24 h urine chloride and magnesium levels and in modification of the diet in renal disease. Mean blood potassium levels increased from 2.8G0.3, 3.5 G0.5 and 3.2G0.3 before treatment to 3.2G0.5, 3.7G0.6 and 3.7G0.3 mmol/l with treatment in groups with two (PZ0.003), one and no mutated alleles respectively. Conclusion: In adult patients referred for renal hypokalaemia, we confirmed the presence of mutations of the SLC12A3 gene in 80% of cases. GS was more severe in patients with two mutated alleles than in those with one or no mutated alleles. High blood pressure should not rule out the diagnosis, especially in older patients.

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Section: Discussionmentioning

confidence: 93%

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Balavoine

Bataille

Vanhille

et al. 2011

European Journal of Endocrinology

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“…The residual function of ENaC when tested in a heterologous system such as the Xenopus system may give some hint on the clinical severity. One patient with a partially inactivating G327C mutation showed significantly less salt-losing crises and had a normalization of the initially elevated plasma renin activity and aldosterone levels over time [63]. On the contrary, patients with a completely inactivating mutation have no normalization of these parameters.…”

Section: Genotype-phenotype Associationsmentioning

confidence: 99%

Clinical and Molecular Features of Type 1 Pseudohypoaldosteronism

2009

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Pseudohypoaldosteronism (PHA) is a rare heterogeneous syndrome of mineralocorticoid resistance causing insufficient potassium and hydrogen secretion. PHA type 1 (PHA1) causes neonatal salt loss, failure to thrive, dehydration and circulatory shock. Two different forms of PHA1 can be distinguished on the clinical and genetic level, showing either a systemic or a renal form of mineralocorticoid resistance. This review provides an overview on transepithelial sodium reabsorption and on clinical features and the underlying molecular pathology of systemic and renal PHA1 caused by mutations in the subunit genes (SCNN1A, SCNN1B, SCNN1G) of the epithelial sodium channel (ENaC) and the mineralocorticoid receptor coding gene NR3C2. The in vitro investigation of several mutants has resulted in important progress in the understanding of the physiology of ENaC and the mineralocorticoid receptor. Some mutations are discussed in more detail to demonstrate some of these findings. A better clinical work-up of the patients suffering from PHA1 may delineate additional associations between the genotype and phenotype in the future.

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“…In view of this model, it is likely that ENaC functions as a heterotrimer composed of ␣, ␤-, and ␥-ENaC (37). Both molecular genetic studies in humans (7,11,38) and in vitro expression studies (6,12,13,31) indicate that all three subunits are essential for ENaC activity.…”

mentioning

confidence: 99%

Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis

Edelheit

Hanukoglu

Dascal

et al. 2011

American Journal of Physiology-Renal Physiology

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Renin–aldosterone response, urinary Na/K ratio and growth in pseudohypoaldosteronism patients with mutations in epithelial sodium channel (ENaC) subunit genes

Cited by 57 publications

References 29 publications

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Phenotype–genotype correlation and follow-up in adult patients with hypokalaemia of renal origin suggesting Gitelman syndrome

Clinical and Molecular Features of Type 1 Pseudohypoaldosteronism

Identification of the roles of conserved charged residues in the extracellular domain of an epithelial sodium channel (ENaC) subunit by alanine mutagenesis

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