title: 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.affiliation: Division of Medical Sciences, Queen Elizabeth Hospital, University of Birmingham, Edgbaston, Birmingham B15 2TH, UK.
authors.forename: M
authors.initials: M
authors.lastname: Quinkler
authors.forename: B
authors.initials: B
authors.lastname: Bappal
authors.forename: N
authors.initials: N
authors.lastname: Draper
authors.forename: A J
authors.initials: AJ
authors.lastname: Atterbury
authors.forename: G G
authors.initials: GG
authors.lastname: Lavery
authors.forename: E A
authors.initials: EA
authors.lastname: Walker
authors.forename: V
authors.initials: V
authors.lastname: DeSilva
authors.forename: N F
authors.initials: NF
authors.lastname: Taylor
authors.forename: S
authors.initials: S
authors.lastname: Hala
authors.forename: N
authors.initials: N
authors.lastname: Rajendra
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002675:Child, Preschool; D003348:Cortisone / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006973:Hypertension / Q000151:congenital / Q000235:genetics* / Q000503:physiopathology*; D007223:Infant; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism*; D009154:Mutation; D009850:Oman; D010375:Pedigree; D011237:Predictive Value of Tests
chemical_list: D008901:Mineralocorticoids; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003348:Cortisone