Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene

Kathleen M. Kayes-Wandover, Grace M. Tannin, Dorothy Shulman, Dror Peled, Kenneth L. Jones, Lefkothea Karaviti, Perrin C. White

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

Original languageEnglish (US)
Pages (from-to)5379-5382
Number of pages4
JournalJournal of Clinical Endocrinology and Metabolism
Volume86
Issue number11
DOIs
StatePublished - 2001

Fingerprint

Hypoaldosteronism
Cytochrome P-450 CYP11B2
Genes
Aldosterone
Mutation
Fludrocortisone
Congenital Adrenal Hyperplasia
Failure to Thrive
Angiotensinogen
Hyperkalemia
Angiotensin Receptors
Gene encoding
Hyponatremia
Biosynthesis
Peptidyl-Dipeptidase A
Renin
Microsatellite Repeats
Signs and Symptoms
Hydrocortisone
Exons

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. / Kayes-Wandover, Kathleen M.; Tannin, Grace M.; Shulman, Dorothy; Peled, Dror; Jones, Kenneth L.; Karaviti, Lefkothea; White, Perrin C.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 86, No. 11, 2001, p. 5379-5382.

Research output: Contribution to journalArticle

Kayes-Wandover, Kathleen M. ; Tannin, Grace M. ; Shulman, Dorothy ; Peled, Dror ; Jones, Kenneth L. ; Karaviti, Lefkothea ; White, Perrin C. / Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene. In: Journal of Clinical Endocrinology and Metabolism. 2001 ; Vol. 86, No. 11. pp. 5379-5382.
@article{77ee2df6a4cd4fa3a0397e8e683f4a0a,
title = "Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene",
abstract = "Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.",
author = "Kayes-Wandover, {Kathleen M.} and Tannin, {Grace M.} and Dorothy Shulman and Dror Peled and Jones, {Kenneth L.} and Lefkothea Karaviti and White, {Perrin C.}",
year = "2001",
doi = "10.1210/jc.86.11.5379",
language = "English (US)",
volume = "86",
pages = "5379--5382",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Congenital hyperreninemic hypoaldosteronism unlinked to the aldosterone synthase (CYP11B2) gene

AU - Kayes-Wandover, Kathleen M.

AU - Tannin, Grace M.

AU - Shulman, Dorothy

AU - Peled, Dror

AU - Jones, Kenneth L.

AU - Karaviti, Lefkothea

AU - White, Perrin C.

PY - 2001

Y1 - 2001

N2 - Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

AB - Isolated hyperreninemic hypoaldosteronism presenting in infancy is usually caused by mutations in the CYP11B2 gene encoding aldosterone synthase. We studied five patients in four unrelated kindreds with hyperreninemic hypoaldosteronism, in whom we were unable to find such mutations. All presented in infancy with failure to thrive, hyponatremia, hyperkalemia, markedly elevated plasma renin activity, and low or inappropriately normal aldosterone levels. All had normal cortisol levels and no signs or symptoms of congenital adrenal hyperplasia. All responded to fludrocortisone treatment. There were no mutations detected in exons or splice junctions of CYP11B2. Linkage of the disorder to CYP11B2 was studied in two unrelated consanguineous patients and in an affected sib pair. The consanguineous patients were each heterozygous for at least one of three polymorphic microsatellite markers near CYP11B2, excluding linkage to CYP11B2. However, linkage of the disease to CYP11B2 could not be excluded in the affected sib pair. Genes involved in the regulation of aldosterone biosynthesis, including those encoding angiotensinogen, angiotensin-converting enzyme, and the AT1 angiotensin II receptor were similarly excluded from linkage. These results demonstrate the existence of an inherited form of hyperreninemic hypoaldosteronism distinct from aldosterone synthase deficiency. The affected gene(s) remain to be determined.

UR - http://www.scopus.com/inward/record.url?scp=0035185578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035185578&partnerID=8YFLogxK

U2 - 10.1210/jc.86.11.5379

DO - 10.1210/jc.86.11.5379

M3 - Article

C2 - 11701710

AN - SCOPUS:0035185578

VL - 86

SP - 5379

EP - 5382

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -