These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Five novel mutations in the SCNN1A gene causing autosomal recessive pseudohypoaldosteronism type 1.
    Author: Welzel M, Akin L, Büscher A, Güran T, Hauffa BP, Högler W, Leonards J, Karges B, Kentrup H, Kirel B, Senses EE, Tekin N, Holterhus PM, Riepe FG.
    Journal: Eur J Endocrinol; 2013 May; 168(5):707-15. PubMed ID: 23416952.
    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.
    [Abstract] [Full Text] [Related] [New Search]