In Vitro Expression Studies of a Novel Mutation Δ299 in a Patient Affected with Apparent Mineralocorticoid Excess

Karen Lin-Su, Ping Zhou, Nimmi Arora, Brian P. Betensky, Maria I. New, Robert C. Wilson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Apparent mineralocorticoid excess syndrome (AME) is an autosomal recessive disorder that results in low renin hypertension and other characteristic clinical features. Typical patients present with severe hypertension, hypokalemia, and undetectable aldosterone. Most patients also have low birth weight, failure to thrive, and nephrocalcinosis. The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) defect is documented by demonstrating a failure to convert cortisol to cortisone. Here, we report a patient with typical phenotypic features of AME who does not carry any of the previously described mutations in the HSDIIB2 gene. This female patient from a consanguineous Pakistani family presented at age 9 yr. She had a low birth weight compared with her siblings and presented with hypertension (225/120 mm Hg), low plasma renin activity, hypokalemic metabolic alkalosis, suppressed aldosterone, and bilateral nephrocalcinosis. Echocardiogram did not reveal left ventricular hypertrophy, and baseline ophthalmological evaluation did not demonstrate hypertensive retinopathy. However, at age 12 yr, she developed mild to moderate hypertensive retinopathy. Biochemical analysis showed an elevated urinary cortisol to cortisone metabolites ratio (tetrahydrocortisol and 5α-tetrahydrocortisol/tetrahydrocortisone) of 28 (normal, 0.66-2.44). She had a cortisol secretion rate of 0.43 mg/d (normal, 5-25 mg/d). Sequence analysis of the HSD11B2 gene revealed a novel homozygous Δ299 mutation in exon 5. In vitro expression in Chinese hamster ovary cells revealed that this mutation resulted in no activity.

Original languageEnglish (US)
Pages (from-to)2024-2027
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Fingerprint

Mineralocorticoids
Tetrahydrocortisol
Hydrocortisone
Apparent Mineralocorticoid Excess Syndrome
Hypertensive Retinopathy
Cortisone
Nephrocalcinosis
Aldosterone
Renin
Mutation
Tetrahydrocortisone
Low Birth Weight Infant
Genes
Hypertension
11-beta-Hydroxysteroid Dehydrogenases
Metabolites
Failure to Thrive
Alkalosis
Hypokalemia
Exons

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

In Vitro Expression Studies of a Novel Mutation Δ299 in a Patient Affected with Apparent Mineralocorticoid Excess. / Lin-Su, Karen; Zhou, Ping; Arora, Nimmi; Betensky, Brian P.; New, Maria I.; Wilson, Robert C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 5, 05.2004, p. 2024-2027.

Research output: Contribution to journalArticle

Lin-Su, Karen ; Zhou, Ping ; Arora, Nimmi ; Betensky, Brian P. ; New, Maria I. ; Wilson, Robert C. / In Vitro Expression Studies of a Novel Mutation Δ299 in a Patient Affected with Apparent Mineralocorticoid Excess. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89, No. 5. pp. 2024-2027.
@article{3bf032c4a3504481b2a621c8284ccba3,
title = "In Vitro Expression Studies of a Novel Mutation Δ299 in a Patient Affected with Apparent Mineralocorticoid Excess",
abstract = "Apparent mineralocorticoid excess syndrome (AME) is an autosomal recessive disorder that results in low renin hypertension and other characteristic clinical features. Typical patients present with severe hypertension, hypokalemia, and undetectable aldosterone. Most patients also have low birth weight, failure to thrive, and nephrocalcinosis. The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) defect is documented by demonstrating a failure to convert cortisol to cortisone. Here, we report a patient with typical phenotypic features of AME who does not carry any of the previously described mutations in the HSDIIB2 gene. This female patient from a consanguineous Pakistani family presented at age 9 yr. She had a low birth weight compared with her siblings and presented with hypertension (225/120 mm Hg), low plasma renin activity, hypokalemic metabolic alkalosis, suppressed aldosterone, and bilateral nephrocalcinosis. Echocardiogram did not reveal left ventricular hypertrophy, and baseline ophthalmological evaluation did not demonstrate hypertensive retinopathy. However, at age 12 yr, she developed mild to moderate hypertensive retinopathy. Biochemical analysis showed an elevated urinary cortisol to cortisone metabolites ratio (tetrahydrocortisol and 5α-tetrahydrocortisol/tetrahydrocortisone) of 28 (normal, 0.66-2.44). She had a cortisol secretion rate of 0.43 mg/d (normal, 5-25 mg/d). Sequence analysis of the HSD11B2 gene revealed a novel homozygous Δ299 mutation in exon 5. In vitro expression in Chinese hamster ovary cells revealed that this mutation resulted in no activity.",
author = "Karen Lin-Su and Ping Zhou and Nimmi Arora and Betensky, {Brian P.} and New, {Maria I.} and Wilson, {Robert C.}",
year = "2004",
month = "5",
doi = "10.1210/jc.2003-031268",
language = "English (US)",
volume = "89",
pages = "2024--2027",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "5",

}

TY - JOUR

T1 - In Vitro Expression Studies of a Novel Mutation Δ299 in a Patient Affected with Apparent Mineralocorticoid Excess

AU - Lin-Su, Karen

AU - Zhou, Ping

AU - Arora, Nimmi

AU - Betensky, Brian P.

AU - New, Maria I.

AU - Wilson, Robert C.

PY - 2004/5

Y1 - 2004/5

N2 - Apparent mineralocorticoid excess syndrome (AME) is an autosomal recessive disorder that results in low renin hypertension and other characteristic clinical features. Typical patients present with severe hypertension, hypokalemia, and undetectable aldosterone. Most patients also have low birth weight, failure to thrive, and nephrocalcinosis. The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) defect is documented by demonstrating a failure to convert cortisol to cortisone. Here, we report a patient with typical phenotypic features of AME who does not carry any of the previously described mutations in the HSDIIB2 gene. This female patient from a consanguineous Pakistani family presented at age 9 yr. She had a low birth weight compared with her siblings and presented with hypertension (225/120 mm Hg), low plasma renin activity, hypokalemic metabolic alkalosis, suppressed aldosterone, and bilateral nephrocalcinosis. Echocardiogram did not reveal left ventricular hypertrophy, and baseline ophthalmological evaluation did not demonstrate hypertensive retinopathy. However, at age 12 yr, she developed mild to moderate hypertensive retinopathy. Biochemical analysis showed an elevated urinary cortisol to cortisone metabolites ratio (tetrahydrocortisol and 5α-tetrahydrocortisol/tetrahydrocortisone) of 28 (normal, 0.66-2.44). She had a cortisol secretion rate of 0.43 mg/d (normal, 5-25 mg/d). Sequence analysis of the HSD11B2 gene revealed a novel homozygous Δ299 mutation in exon 5. In vitro expression in Chinese hamster ovary cells revealed that this mutation resulted in no activity.

AB - Apparent mineralocorticoid excess syndrome (AME) is an autosomal recessive disorder that results in low renin hypertension and other characteristic clinical features. Typical patients present with severe hypertension, hypokalemia, and undetectable aldosterone. Most patients also have low birth weight, failure to thrive, and nephrocalcinosis. The 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) defect is documented by demonstrating a failure to convert cortisol to cortisone. Here, we report a patient with typical phenotypic features of AME who does not carry any of the previously described mutations in the HSDIIB2 gene. This female patient from a consanguineous Pakistani family presented at age 9 yr. She had a low birth weight compared with her siblings and presented with hypertension (225/120 mm Hg), low plasma renin activity, hypokalemic metabolic alkalosis, suppressed aldosterone, and bilateral nephrocalcinosis. Echocardiogram did not reveal left ventricular hypertrophy, and baseline ophthalmological evaluation did not demonstrate hypertensive retinopathy. However, at age 12 yr, she developed mild to moderate hypertensive retinopathy. Biochemical analysis showed an elevated urinary cortisol to cortisone metabolites ratio (tetrahydrocortisol and 5α-tetrahydrocortisol/tetrahydrocortisone) of 28 (normal, 0.66-2.44). She had a cortisol secretion rate of 0.43 mg/d (normal, 5-25 mg/d). Sequence analysis of the HSD11B2 gene revealed a novel homozygous Δ299 mutation in exon 5. In vitro expression in Chinese hamster ovary cells revealed that this mutation resulted in no activity.

UR - http://www.scopus.com/inward/record.url?scp=2442417504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2442417504&partnerID=8YFLogxK

U2 - 10.1210/jc.2003-031268

DO - 10.1210/jc.2003-031268

M3 - Article

C2 - 15126515

AN - SCOPUS:2442417504

VL - 89

SP - 2024

EP - 2027

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -