A frameshift mutation of β subunit of epithelial sodium channel in a case of isolated Liddle syndrome

Background: Liddle syndrome is an autosomal dominant form of salt-sensitive hypertension caused by mutations in the epithelial sodium channel expressed in the distal nephron playing an essential role in Na⁺ absorption. All reported mutations in Liddle syndrome are either missense mutations or frameshift mutations destroying the PY motif closer to the C-terminus of the β or γ subunits causing the situation that the epithelial sodium channels are not degraded and sodium is pooled and thus hypertension and hypokalemia are caused. Methods: We sequenced the C-terminus of the β or γ subunits of the epithelial sodium channel in a Japanese family of a patient clinically diagnosed as having Liddle syndrome. Results: As a result, we found in the proband, a frameshift mutation of the β subunit caused by a single cytosine insertion at the codon 595, introducing a new stop codon at 605 and deleting the last 34 amino acids from the normally encoded protein. Conclusion: This mutation is carried by neither parent (with paternity proven) and hence confirms this has occurred as a de novo event within this family.