Apparent mineralocorticoid excess (AME) is a rare autosomal recessive genetic disorder causing severe hypertension in childhood due to a deficiency of 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2), which is encoded by HSD11B2. Without treatment, chronic hypertension leads to early development of end-organ damage. Approximately 40 causative mutations in HSD11B2 have been identified in â¼100 AME patients worldwide. We have studied the clinical presentation, biochemical parameters, and molecular genetics in six patients from a consanguineous Omani family with AME. DNA sequence analysis of affected members of this family revealed homozygous c.799A>G mutations within exon 4 of HSD11B2, corresponding to a p.T267A mutation of 11ßHSD2. The structural change and predicted consequences owing to the p.T267A mutation have been modeled in silico. We conclude that this novel mutation is responsible for AME in this family.
11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics , Mineralocorticoid Excess Syndrome, Apparent/enzymology , Mineralocorticoid Excess Syndrome, Apparent/genetics , Mutation/genetics , 11-beta-Hydroxysteroid Dehydrogenase Type 2/chemistry , Amino Acid Sequence , Base Sequence , Child, Preschool , Computer Simulation , DNA Mutational Analysis , Family , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Models, Molecular , Oman , Mineralocorticoid Excess Syndrome, Apparent
