title: A novel mutation in HSD11B2 causes apparent mineralocorticoid excess in an Omani kindred.
abstract: Apparent mineralocorticoid excess (AME) is a rare autosomal recessive genetic disorder causing severe hypertension in childhood due to a deficiency of 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2), 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 ∼100 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 11βHSD2. 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.
authors.affiliation: Department of Pediatrics and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. mabel.yau@mssm.edu.
authors.forename: Mabel
authors.initials: M
authors.lastname: Yau
authors.affiliation: Department of Pediatrics, The Royal Hospital, Muscat, Oman.
authors.forename: Hanan Said Al
authors.initials: HS
authors.lastname: Azkawi
authors.affiliation: Department of Pharmaceutical and Biological Chemistry, University College London School of Pharmacy, London, United Kingdom.
authors.forename: Shozeb
authors.initials: S
authors.lastname: Haider
authors.affiliation: Department of Pediatrics and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khattab
authors.affiliation: Department of Pediatrics, The Royal Hospital, Muscat, Oman.
authors.forename: Maryam Al
authors.initials: MA
authors.lastname: Badi
authors.affiliation: Department of Pediatrics, The Royal Hospital, Muscat, Oman.
authors.forename: Wafa
authors.initials: W
authors.lastname: Abdullah
authors.affiliation: Department of Pediatrics, The Royal Hospital, Muscat, Oman.
authors.forename: Aisha Al
authors.initials: AA
authors.lastname: Senani
authors.affiliation: Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wilson
authors.affiliation: Department of Pediatrics and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Tony
authors.initials: T
authors.lastname: Yuen
authors.affiliation: Department of Pediatrics and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
authors.affiliation: Department of Pediatrics and Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Maria I
authors.initials: MI
authors.lastname: New
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D003198:Computer Simulation; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D043204:Mineralocorticoid Excess Syndrome, Apparent / Q000201:enzymology* / Q000235:genetics*; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics*; D009850:Oman
chemical_list: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human
keywords: computational modeling; in silico mutation analysis; low-renin hypertension; molecular genetics