Molecular basis for the apparent mineralocorticoid excess syndrome in the Oman population.

Abstract

11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) plays a crucial role in converting hormonally active cortisol to inactive cortisone, thereby conferring specificity upon the mineralocorticoid receptor (MR). Mutations in the gene encoding 11beta-HSD2 (HSD11B2) account for an inherited form of hypertension, the syndrome of "Apparent Mineralocorticoid Excess" (AME) where cortisol induces hypertension and hypokalaemia. We report five different mutations in the HSD11B2 gene in four families from Oman with a total of 9 affected children suffering from AME. Sequence data demonstrate the previously described L114Delta6nt mutation in exon 2 and new mutations in exon 3 (A221V), exon 5 (V322ins9nt) and for the first time in exon 1 (R74G and P75Delta1nt) of the HSD11B2 gene. These additional mutations provide further insight into AME and the function of the 11beta-HSD2 enzyme. The prevalence of monogenic forms of hypertension such as AME remains uncertain. However, our data suggests AME may be a relevant cause of hypertension in certain ethnic groups, such as the Oman population.

• Authors: M Quinkler, B Bappal, N Draper, A J Atterbury, G G Lavery, E A Walker, V DeSilva, N F Taylor, S Hala, N Rajendra, P M Stewart
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 217 Issue 1-2 Pg. 143-9 (Mar 31 2004) ISSN: 0303-7207 [Print] Ireland
• PMID: 15134813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mineralocorticoids
• 11-beta-Hydroxysteroid Dehydrogenases
• Cortisone

Topics

• 11-beta-Hydroxysteroid Dehydrogenases (genetics, metabolism)
• Case-Control Studies
• Child, Preschool
• Cortisone (metabolism)
• Exons (genetics)
• Female
• Genetic Predisposition to Disease
• Humans
• Hypertension (congenital, genetics, physiopathology)
• Infant
• Male
• Mineralocorticoids (metabolism)
• Mutation
• Oman
• Pedigree
• Predictive Value of Tests