This Article Full Text Full Text (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 Nyström, A.-M. Articles by Annerén, G. Search for Related Content PubMed PubMed Citation Articles by Nyström, A.-M. Articles by Annerén, G.

A Novel Nonsense Mutation of the Mineralocorticoid Receptor Gene in a Swedish Family with Pseudohypoaldosteronism Type I (PHA1)

Departments of Genetics and Pathology (A.-M.N., M.-L.B., J.M., G.A.) and Women’s and Children’s Health (B.S., J.G.), Uppsala University, S-751 85 Uppsala, Sweden; and Department of Pediatrics (N.S.), Central Hospital of Eskilstuna, S-637 88 Eskilstuna, Sweden

Address all correspondence and requests for reprints to: Professor Göran Annerén, M.D., Department of Clinical Genetics, Uppsala University Children’s Hospital, S-751 85 Uppsala, Sweden. E-mail: goran.anneren{at}genpat.uu.se.

Pseudohypoaldosteronism type I (PHA1) is a condition associated with salt wasting leading to dehydration, hypotension, hyperkalemia, and metabolic acidosis. Sporadic cases and two familial forms, one autosomal dominant and one autosomal recessive form, have been described. The autosomal dominant or sporadic form manifests milder salt wasting that remits with age. Mutations in the gene encoding the mineralocorticoid receptor (MR) have been identified in patients with the autosomal dominant inheritance. However, recent studies suggest that the autosomal dominant and sporadic forms are genetically heterogeneous and that additional genes might be involved. We report on the study of 15 members of a Swedish five-generation family with the autosomal dominant form of PHA1. Interestingly, neuropathy was found in two of five affected individuals. A novel heterozygous nonsense mutation C436X in exon 2 was identified in the index patient by linkage analysis, PCR, and direct sequencing of the MR gene. Analysis of the family demonstrated that the mutation segregated with PHA1 in the family. It is unclear whether the neuropathy is associated with the mutation found. Our results together with previously published data suggest that loss-of-function mutations of the MR gene located at 4q31.1, commonly are associated with the autosomal dominant form of PHA1.

This work was supported by grants from the Beijer Foundation and the Marcus Borgström Foundation.

Abbreviations: ENaC, Amiloride-sensitive luminal sodium channel; MR, mineralocorticoid receptor; PHA1, pseudohypoaldosteronism type I.

This article has been cited by other articles:

				C. Ronzaud, J. Loffing, M. Bleich, N. Gretz, H.-J. Grone, G. Schutz, and S. Berger Impairment of Sodium Balance in Mice Deficient in Renal Principal Cell Mineralocorticoid Receptor J. Am. Soc. Nephrol., June 1, 2007; 18(6): 1679 - 1687. [Abstract] [Full Text] [PDF]

				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]

				F. L. Fernandes-Rosa, M. de Castro, A. C. Latronico, W. G. Sippell, F. G. Riepe, and S. R. Antonini 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 J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3671 - 3675. [Abstract] [Full Text] [PDF]

				D. S. Geller, J. Zhang, M.-C. Zennaro, A. Vallo-Boado, J. Rodriguez-Soriano, L. Furu, R. Haws, D. Metzger, B. Botelho, L. Karaviti, et al. Autosomal Dominant Pseudohypoaldosteronism Type 1: Mechanisms, Evidence for Neonatal Lethality, and Phenotypic Expression in Adults J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1429 - 1436. [Abstract] [Full Text] [PDF]