Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1

Maik Welzel, Leyla Akin, Anja Büscher, Tülay Güran, Berthold P Hauffa, Wolfgang Högler, Julia Leonards, Beate Karges, Heiner Kentrup, Birgul Kirel, Emine Esin Yalinbas Senses, Neslihan Tekin, Paul-Martin Holterhus, Felix G Riepe

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

BACKGROUND: Pseudohypoaldosteronism type 1 (PHA1) is a monogenic disease caused by mutations in the genes encoding the human mineralocorticoid receptor (MR) or the α (SCNN1A), β (SCNN1B) or γ (SCNN1G) subunit of the epithelial Na(+) channel (ENaC). While autosomal dominant mutation of the MR cause renal PHA1, autosomal recessive mutations of the ENaC lead to systemic PHA1. In the latter, affected children suffer from neonatal onset of multi-organ salt loss and often exhibit cystic fibrosis-like pulmonary symptoms.

OBJECTIVE: We searched for underlying mutations in seven unrelated children with systemic PHA1, all offsprings of healthy consanguineous parents.

METHODS AND RESULTS: Amplification of the SCNN1A gene and sequencing of all 13 coding exons unraveled mutations in all of our patients. We found five novel homozygous mutations (c.587_588insC in two patients, c.1342_1343insTACA, c.742delG, c.189C>A, c.1361-2A>G) and one known mutation (c.1474C>T) leading to truncation of the αENaC protein. All parents were asymptomatic heterozygous carriers of the respective mutations, confirming the autosomal recessive mode of inheritance. Five out of seven patients exhibited pulmonary symptoms in the neonatal period.

CONCLUSION: The α subunit is essential for ENaC function and mutations truncating the pore-forming part of the protein leading to systemic PHA1. Based on current knowledge, the pulmonary phenotype cannot be satisfactorily predicted.

Original languageEnglish
Pages (from-to)707-15
Number of pages9
JournalEuropean Journal of Endocrinology
Volume168
Issue number5
DOIs
Publication statusPublished - May 2013

Keywords

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Epithelial Sodium Channels
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mutation
  • Pedigree
  • Phenotype
  • Pseudohypoaldosteronism
  • Case Reports
  • Journal Article

Fingerprint

Dive into the research topics of 'Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1'. Together they form a unique fingerprint.

Cite this