title: Identification of a novel mutation in the human mineralocorticoid receptor gene in a german family with autosomal-dominant pseudohypoaldosteronism type 1: further evidence for marked interindividual clinical heterogeneity.
abstract: Pseudohypoaldosteronism (PHA) type 1 presents in infancy with potential life-threatening salt wasting and failure to thrive. Plasma renin activity and aldosterone levels are markedly elevated. PHA1 is inherited in either an autosomal recessive or autosomal dominant trait. The autosomal dominant form manifests with renal salt loss in infancy and a gradual improvement with advancing age. We report the case of a renal form of PHA1 in a German family. PCR and direct sequencing revealed a heterozygous point mutation, c488C>G (S163X), leading to a premature stop codon in the index patient. The segregation analysis revealed the identical mutation in the patient's father, who showed no symptoms of PHA at the time of investigation or before. The family was screened for amino acid polymorphisms in the amiloride-sensitive epithelial sodium channel, which could be a cause for phenotypic differences within the family. PCR and direct sequencing revealed identical epithelial sodium channel haplotypes in the patient and his father. These polymorphisms can, therefore, not be responsible for the difference in clinical presentation. It remains to be elucidated whether other defects or polymorphisms in genes coding for regulatory proteins participating in sodium homeostasis are a cause of the heterogeneity of the clinical manifestations in autosomal dominant PHA1.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, Christian Albrechts University Kiel, Germany.
authors.forename: Felix G
authors.initials: FG
authors.lastname: Riepe
authors.forename: Nils
authors.initials: N
authors.lastname: Krone
authors.forename: Michel
authors.initials: M
authors.lastname: Morlot
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Wolfgang G
authors.initials: WG
authors.lastname: Sippell
authors.forename: Carl-Joachim
authors.initials: CJ
authors.lastname: Partsch
mesh_terms: D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D053503:Epithelial Sodium Channels; D005858:Germany; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011546:Pseudohypoaldosteronism / Q000235:genetics*; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D015222:Sodium Channels / Q000235:genetics
chemical_list: D053503:Epithelial Sodium Channels; D018161:Receptors, Mineralocorticoid; D015222:Sodium Channels; D015252:Deoxyribonucleases, Type II Site-Specific; C024405:GATC-specific type II deoxyribonucleases