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

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...

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Bibliographic Details
Published in:	The journal of clinical endocrinology and metabolism Vol. 89; no. 1; pp. 227 - 231
Main Authors:	Nyström, A.-M., Bondeson, M.-L., Skanke, N., Mårtensson, J., Strömberg, B., Gustafsson, J., Annerén, G.
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Endocrine Society 01-01-2004 Copyright by The Endocrine Society
Subjects:	Adult Aged Biologi Biological and medical sciences Biology Cell and molecular biology Cell- och molekylärbiologi Child Chromosomes, Human, Pair 12 Chromosomes, Human, Pair 16 Chromosomes, Human, Pair 4 Codon, Nonsense - genetics Endocrinopathies Exons Female Fundamental and applied biological sciences. Psychology Genetic Linkage Genetics Genetik Humans Linkage (Genetics) Male Medical sciences Middle Aged NATURAL SCIENCES NATURVETENSKAP Pedigree Polymerase Chain Reaction Polymorphism, Restriction Fragment Length Pseudohypoaldosteronism - genetics Receptors, Mineralocorticoid - genetics Sequence Analysis, DNA Sweden Vertebrates: endocrinology Sweden Europe Endocrinopathy Kidney disease Urinary system disease Steroid hormone Mineralocorticoid Nonsense mutation Tubulopathy Aldosterone Target tissue resistance Pseudohypoaldosteronism Adrenal hormone Multigene family Endocrinology Biological receptor Human Pair 4 Research Support Nonsense/genetics Restriction Fragment Length Mineralocorticoid/genetics Receptors Pair 12 Codon DNA Sequence Analysis Chromosomes Non-U.S. Gov't Pair 16 Polymorphism
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Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0021-972X 1945-7197
DOI:	10.1210/jc.2003-030762