Document Detail


Glucocorticoid remediable aldosteronism: low morbidity and mortality in a four-generation italian pedigree.
MedLine Citation:
PMID:  12107222     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucocorticoid remediable hyperaldosteronism (GRA) is a monogenic form of inherited hypertension caused by a chimeric gene originating from an unequal cross-over between the 11 beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes. GRA is characterized by high plasma levels of aldosterone (regulated by ACTH) with suppressed plasma renin activity and the production of two rare steroids, 18hydroxycortisol and 18oxocortisol. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Affected women have a high risk of developing preeclampsia during pregnancy. Here, we describe a 5-generation pedigree from Sardinia in which the presence of the chimeric gene is demonstrated in 4 generations. This family displays a mild phenotype with average blood pressure levels of 131/86 mm Hg for GRA+ patients. The occurrence of stroke is very low, and preeclampsia was not observed in 29 pregnancies from 8 GRA+ mothers. We investigated whether the cross-over site (between the CYP11B1 and CYP11B2 genes) or biochemical characteristics could explain this phenotype. The cross-over site was located at the end of intron 3, in the same region as described in other families. We found a significant correlation between blood pressure and 18hydroxycortisol, 18oxocortisol, and plasma aldosterone levels, but not with kallikrein. However, none of the biochemical or genetic parameters investigated could explain the mild phenotype of the family.
Authors:
Paolo Mulatero; Stefania Morra di Cella; Tracy A Williams; Alberto Milan; Giulio Mengozzi; Livio Chiandussi; Celso E Gomez-Sanchez; Franco Veglio
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  87     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-10     Completed Date:  2002-08-02     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3187-91     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine and Experimental Oncology, Hypertension Unit, San Vito Hospital, University of Turin, Strada San Vito 34, 10133 Turin, Italy. paolo.mulatero@libero.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Aldosterone / blood
Aldosterone Synthase / genetics
Blood Pressure
Crossing Over, Genetic
Female
Glucocorticoids / therapeutic use*
Humans
Hydrocortisone / analogs & derivatives*,  blood
Hyperaldosteronism / drug therapy*,  genetics*,  mortality,  physiopathology
Italy
Male
Middle Aged
Pedigree
Phenotype
Pregnancy
Pregnancy Complications / physiopathology
Steroid 11-beta-Hydroxylase / genetics
Chemical
Reg. No./Substance:
0/Glucocorticoids; 2410-60-8/18-oxocortisol; 50-23-7/Hydrocortisone; 52-39-1/Aldosterone; 81705-06-8/18-hydroxycortisol; EC 1.14.15.4/Aldosterone Synthase; EC 1.14.15.4/Steroid 11-beta-Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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