Mutations in the carboxy terminus of the β and γ subunits of the epithelial sodium channel are not present in patients with hypertensive crisis

Födinger, Manuela; Hirschl, MM; Schedler, Dagmar; Herkner, Harald; Bur, Andreas; Laggner, Anton N.; Hörl, Walter H.; Sunder‐Plassmann, Gere

doi:10.1046/j.1365-2362.1998.00369.x

Cited by 8 publications

(1 citation statement)

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“…Although the number of patients suffering from classic ‘Liddle’ is extremely low, recent evidence for functionally relevant mutations in the ENaC has been demonstrated in black ‘essential’ hypertensives, indicating that this mutation is the most frequent cause of secondary hypertension in this population [8]. The lack of association between molecular variants of either the β- or γ-subunit of the ENaC and hypertension in unselected hypertensive patients [77, 78]suggests that careful patient selection based on phenotypical characteristics, such as plasma renin levels or salt sensitivity, may be crucial in order to increase the probability to detect such mutations. For instance, hypertensive patients with a marked response to a therapy with amiloride represent an ideal target; however, these subjects have not been systematically investigated so far and therefore represent a candidate group for genetic analysis.…”

Section: Mutations In the Epithelial Sodium Channel Genesmentioning

confidence: 99%

Juvenile Hypertension, the Role of Genetically Altered Steroid Metabolism

2001

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The importance of hypertension in the pediatric population is not as well appreciated as in adults. This might be related in part to the lower prevalence of high blood pressure in this age group. As with height and weight, blood pressure increases with age during childhood. The underlying causes of significant hypertension in children differ considerably from those in adults: while the prevalence of hypertension in pediatrics is lower than in adults, clinically identifiable causes of hypertension are common. Abnormalities in steroid biosynthesis have been known for years to cause hypertension in some cases of congenital adrenal hyperplasia. In these patients, hypertension usually accompanies a characteristic phenotype with abnormal sexual differentiation. Recently, the molecular basis of four forms of severe hypertension transmitted on an autosomal basis has been elucidated: (a) the glucocorticoid-remediable aldosteronism (GRA), (b) the syndrome of apparent mineralocorticoid excess (AME), (c) activating mutation of the mineralocorticoid receptor and (d) Liddle’s syndrome. All these conditions are characterized primarily by low or low-normal plasma renin, normal or low serum potassium and salt-sensitive hypertension, indicating an increased mineralocorticoid effect. These forms of juvenile hypertension are a consequence of abnormal biosynthesis, metabolism or action of steroid hormones: (a) GRA is due to expression of a chimeric gene produced by fusion of 11β-hydroxylase aldosterone-synthase genes. Expression of the chimeric enzyme occurs in the zona fasciculata of the adrenal cortex under the control of ACTH and can be suppressed by administration of glucocorticoids. (b) AME is caused by mutations of the 11β-hydroxysteroid dehydrogenase type 2 enzyme, an enzyme that metabolizes cortisol into its receptor inactive keto-form cortisone, thus protecting the mineralocorticoid receptor (MR) from occupation by glucocorticoids. (c) The activating mutation of the MR results in constitutive MR activity and alters receptor specificity, with progesterone and other steroids lacking 21-hydroxyl groups becoming potent agonists. (d) Liddle’s syndrome is due to mutations in the β or γ chain of the epithelial sodium channel in distal renal tubule cells. The hyperactivity of this channel caused by the mutations results in increased sodium reabsorption. With the advent of molecular biology in clinical practice it has become evident that some genetic defect may present with a more discrete phenotype, with only moderate hypertension with or without hypokalemia as presenting feature. Considering that hypertension in children and adolescents is often ‘nonessential’, a search for disorders should be integral part of the diagnostic work-up in young patients with hypertension.

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Section: Mutations In the Epithelial Sodium Channel Genesmentioning

confidence: 99%