Whorwood CB, Gupta A, Krozowski Z, Stewart PM
Human hypertension caused by a single point mutation in the type 2
11-beta-hydroxysteroid dehydrogenase (h11 b-HSD2) gene
16th Scientific Meeting of the International Society of Hypertension
ISH Abstract Book
(Jun) 16: 1996
Severe low renin/low aldosterone hypertension with hypokalemia can
arise from congenital deficiency of h11 b-HSD (referred to as the
Syndrome of Apparent Mineralocorticoid Excess (AME)), where the
resulting impaired conversion of cortisol (F) to hormonally inactive
cortisone (E) allows F to preferentially occupy the mineralocorticoid
receptor. Two kinetically distinct isoforms of h11 b-HSD have now been
characterized and cloned. The h11 b-HSD1 gene is, however, normal in
AME patients.
This study reports the sequence and the expression analysis of the
h11 b-HSD2 gene in an Asian kindred with AME. The study revealed a
consistent single C r T mutation at nt1228 of the cDNA, which converts
Arg (CGA) to a premature stop (TGA) at codon 374 in exon 5. No
mutations were evident elsewhere in the gene. The resulting truncated
h11 b-HSD2 protein lacks the proline-rich C-terminal 32 amino acids.
Hypertension in this kindred was caused by a premature-stop codon in
exon 5 of the h11 b-HSD2 gene.
Comment: This establishes AME alongside
glucocorticoid-suppressible hyperaldosteronism & Liddle's syndrome as
examples of monogenic causes of hypertension (Carmine Zoccali,
M.D, Reggio Calabria, Italy).
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16th Scientific Meeting of the International Society of Hypertension
H: Pathophysiology :
Genetics
H: Special problems :
Endocrine hypertension