A novel mutation in HSD11B2 causes apparent mineralocorticoid excess in an Omani kindred

• Published in: Annals of the New York Academy of Sciences Vol. 1376; no. 1; pp. 65 - 71
• Main Authors: Yau, Mabel, Azkawi, Hanan Said Al, Haider, Shozeb, Khattab, Ahmed, Badi, Maryam Al, Abdullah, Wafa, Senani, Aisha Al, Wilson, Robert C., Yuen, Tony, Zaidi, Mone, New, Maria I.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.07.2016; Wiley Subscription Services, Inc
• Subjects: 11-beta-Hydroxysteroid Dehydrogenase Type 2 - chemistry; 11-beta-Hydroxysteroid Dehydrogenase Type 2 - genetics; Amino Acid Sequence; Base Sequence; Child, Preschool; computational modeling; Computer Simulation; DNA Mutational Analysis; Family; Female; Follow-Up Studies; Genes; Humans; Hypertension; in silico mutation analysis; Infant; Infant, Newborn; low-renin hypertension; Male; Mineralocorticoid Excess Syndrome, Apparent; Mineralocorticoid Excess Syndrome, Apparent - enzymology; Mineralocorticoid Excess Syndrome, Apparent - genetics; Models, Molecular; molecular genetics; Mutation; Mutation - genetics; Oman; molecular genetics; in silico mutation analysis; computational modeling; low-renin hypertension
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.13162

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.