Disease relevance of Pseudohypoaldosteronism

• Mutations in the kinase WNK4 cause pseudohypoaldosteronism type II (PHAII), a disease featuring hypertension and hyperkalemia [1].
• Mutations in the WNK4 gene cause pseudohypoaldosteronism type II (PHAII), an autosomal-dominant disorder of hyperkalemia and hypertension [2].
• However, in vivo, adult betaENaC m/m mice exhibited a significantly reduced ENaC activity in colon and elevated plasma aldosterone levels, suggesting hypovolemia and pseudohypoaldosteronism type 1 [3].
• Twenty one patients with selective aldosterone deficiency due to type 2 corticosterone methyl-oxidase defect [hypoaldosteronism (HA)] and 7 with pseudohypoaldosteronism (PHA) were studied longitudinally for up to 18 yr [4].
• We have analyzed the human mineralocorticoid receptor (hMR) gene in 14 families with autosomal dominant or sporadic pseudohypoaldosteronism (PHA1), a rare form of mineralocorticoid resistance characterized by neonatal renal salt wasting and failure to thrive [5].

High impact information on Pseudohypoaldosteronism

• Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I [6].
• Increased chloride reabsorption as an inherited renal tubular defect in familial type II pseudohypoaldosteronism [7].
• Aldosterone-receptor deficiency in pseudohypoaldosteronism [8].
• A mutation causing pseudohypoaldosteronism type 1 identifies a conserved glycine that is involved in the gating of the epithelial sodium channel [9].
• Intronic deletions in the WNK1 gene result in its overexpression and lead to pseudohypoaldosteronism type II, a disease with salt-sensitive hypertension and hyperkalemia [10].

Chemical compound and disease context of Pseudohypoaldosteronism

• Mutations in the serine-threonine kinase WNK4 [with no lysine (K) 4] cause pseudohypoaldosteronism type II, a Mendelian disease featuring hypertension with hyperkalemia [11].
• In CRD1, one of the cysteines of the rat alphaENaC subunit (Cys158) is homologous to Cys133 of the corresponding human subunit causing, when mutated to tyrosine (C133Y), pseudohypoaldosteronism type 1, a severe salt-loosing syndrome in neonates [12].
• The cause was a combination of idiopathic secretion of antidiuretic hormone and distal tubular degeneration resulting in pseudohypoaldosteronism [13].
• BACKGROUND: In mice, a partial loss of function of the epithelial sodium channel (ENaC), which regulates sodium excretion in the distal nephron, causes pseudohypoaldosteronism, a salt-wasting syndrome [14].
• Nephrocalcinosis in pseudohypoaldosteronism and the effect of indomethacin therapy [15].

Biological context of Pseudohypoaldosteronism

• Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis [16].
• A novel missense mutation of mineralocorticoid receptor gene in one Japanese family with a renal form of pseudohypoaldosteronism type 1 [17].
• Hypoaldosteronism may be due to inadequate stimulation of aldosterone secretion (hyporeninemic hypoaldosteronism), defects in adrenal synthesis of aldosterone, or resistance to the ion transport effects of aldosterone, such as are seen in pseudohypoaldosteronism type I (PHA I) [18].
• We have studied the molecular structure of the mineralocorticoid receptor (MR) complementary DNA (cDNA) in a kindred affected by pseudohypoaldosteronism (PHA) [19].
• Systemic pseudohypoaldosteronism from deletion of the promoter region of the human Beta epithelial na(+) channel subunit [20].

Anatomical context of Pseudohypoaldosteronism

• In this study, we investigated nongenomic aldosterone action in five patients with pseudohypoaldosteronism with regard to a rapid increase of free intracellular calcium [Ca2+]i in cultured nasal epithelial cells, assumably reflecting calcium influx through calcium channels [21].
• Finally, functional hypermineralocorticism was associated with reduced expression of hMR beta in sweat glands of two patients affected by Conn's and Liddle's syndrome, whereas normal levels of hMR isoforms were found in one case of pseudohypoaldosteronism [22].
• The affinity and the capacity of mineralocorticoid receptors (MR) in human mononuclear leukocytes (HML) were determined in 9 patients with Conn's syndrome (PA) and in 3 patients with pseudohypoaldosteronism (PHA) [23].
• The membrane-bound Na,K ATPase activity and the transmembrane Na and K transport systems have been studied in vitro in red blood cells of two subjects, son and mother, affected by pseudohypoaldosteronism with different degrees of clinical involvement [24].

Gene context of Pseudohypoaldosteronism

• The WNK1 and WNK4 genes have been found to be mutated in some patients with hyperkalemia and hypertension caused by pseudohypoaldosteronism type II [25].
• Of the four human WNK family members, WNK1 and WNK4 have been linked to a hereditary form of hypertension, pseudohypoaldosteronism type II [26].
• It is of interest that this region also contains Wnk4, a gene previously identified to cause pseudohypoaldosteronism type II and human hypertension [27].
• During the first week of life, MR-deficient (-/-) mice developed symptoms of pseudohypoaldosteronism [28].
• Normal CFTR Activity and Reversed Skin Potentials in Pseudohypoaldosteronism [29].

References