This Article Full Text Full Text (PDF) All Versions of this Article: 91/9/3671    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fernandes-Rosa, F. L. Articles by Antonini, S. R. Search for Related Content PubMed PubMed Citation Articles by Fernandes-Rosa, F. L. Articles by Antonini, S. R. Related Collections Adrenal and Hypertension Cardiovascular Endocrinology

Recurrence of the R947X Mutation in Unrelated Families with Autosomal Dominant Pseudohypoaldosteronism Type 1: Evidence for a Mutational Hot Spot in the Mineralocorticoid Receptor Gene

Division of Pediatric Endocrinology (F.L.F.-R., M.d.C., A.C.L., S.R.A.), Department of Pediatrics, School of Medicine of Ribeirao Preto, University of Sao Paulo, 14049-900 Sao Paulo, Brazil; and Division of Pediatric Endocrinology (W.G.S., F.G.R.), Department of Pediatrics, University Hospital Schleswig-Holstein, Campus Kiel, 24105 Kiel, Germany

Address all correspondence and requests for reprints to: Sonir R. Antonini, M.D., Ph.D., Department of Pediatrics, School of Medicine of Ribeirão Preto, Avenida Bandeirantes, 3900-Ribeirão Preto, 14049-900 Sao Paulo, Brazil. E-mail: s.antonini{at}hcrp.fmrp.usp.br.

Background: The renal form of pseudohypoaldosteronism type 1 (PHA1) is a rare disease characterized by congenital mineralocorticoid resistance of the kidney. Twenty-two different loss-of-function mutations in the mineralocorticoid receptor gene have been described in families with PHA1. These mutations were not recurrent and resulted in a large phenotypic variability.

Objective: The objective of this study is to analyze the recurrence of an inactivating mutation in the mineralocorticoid receptor gene in unrelated families with autosomal dominant PHA1.

Patients: Seventeen members from three unrelated families with autosomal dominant PHA1 were studied, including 11 affected patients with variable clinical manifestations. Fifty healthy subjects were used as controls.

Methods: Genomic DNA was extracted, and the entire coding region of the mineralocorticoid receptor gene was submitted to automatic sequencing. Four dinucleotide microsatellite markers spanning a region of 3.2 cM in the human mineralocorticoid receptor gene locus, and two intragenic polymorphisms were used for haplotype analysis.

Results: A heterozygous point mutation at codon 947 (c.2839C>T) changing arginine to stop codon (R947X) was found in the three families. Different haplotypes segregated with the R947X mutation in each family, demonstrating the absence of a founder effect for this mutation.

Conclusion: Codon 947 of the mineralocorticoid receptor is the first mutational hot spot for autosomal dominant PHA1.

This article has been cited by other articles:

				A. Balsamo, A. Cicognani, M. Gennari, W. G Sippell, S. Menabo, F. Baronio, and F. G Riepe Functional characterization of naturally occurring NR3C2 gene mutations in Italian patients suffering from pseudohypoaldosteronism type 1 Eur. J. Endocrinol., February 1, 2007; 156(2): 249 - 256. [Abstract] [Full Text] [PDF]