Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
J Clin Endocrinol Metab. 2002 Jul;87(7):3344-50.

Novel mutations responsible for autosomal recessive multisystem pseudohypoaldosteronism and sequence variants in epithelial sodium channel alpha-, beta-, and gamma-subunit genes.

Author information

  • 1Department of Chemical Engineering and Biotechnology, The College of Judea and Samaria, Ariel 44837, Israel.

Abstract

Multisystem pseudohypoaldosteronism (PHA), is a syndrome of unresponsiveness to aldosterone with autosomal recessive inheritance. Previously we showed that mutations in the epithelial sodium channel (ENaC) alpha-, beta-, and gamma-subunits are responsible for PHA. In this study we examined four independent probands with multisystem PHA, three of whom were born to consanguineous parents. In our search for mutations we also determined the complete coding sequences of each of the three genes encoding alpha-, beta-, and gamma-subunits in individuals representing different ethnic groups. Our analyses revealed the following homozygous mutations in three probands: 1) insertion of a T in exon 8 of the alpha ENaC gene that causes a frameshift error at Tyr(447) and leads to a premature stop codon at K459 in a Pakistani patient; 2) R508stop mutation in exon 11 of the alpha ENaC gene in an Indian patient; and 3) a splice site mutation in intron 12 of the beta ENaC gene (1669 + 1 g-->a) in a Scottish patient. The parents were heterozygous for the latter two mutations. The second mutation was previously observed in an Iranian Jewish patient. Our sequencing of the alpha-, beta-, and gamma-coding sequences revealed some sequence variants, some of which may represent single nucleotide polymorphisms. The gamma-subunit protein sequence was completely conserved in the six subjects examined. The homozygous mutations identified in the alpha and beta ENaC genes should result in reduced or abolished ENaC activity in PHA patients, explaining the disease symptoms.

PMID:
12107247
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Atypon
    Loading ...
    Write to the Help Desk