A novel epithelial sodium channel gamma-subunit de novo frameshift mutation leads to Liddle syndrome.

OBJECTIVE: Liddle syndrome is a rare autosomal-dominant monogenic form of hypertension caused by mutations in the C-termini of the epithelial sodium channel beta- or gamma-subunit encoded by SCNN1B and SCNN1G, respectively, and often presenting with a familial history of hypertension. The purpose of this study was to determine whether mutations of SCNN1B or SCNN1G were present in a patient clinically suspected to have Liddle syndrome with no familial history of hypertension. DESIGN AND PATIENTS: We screened the C-terminus of SCNN1B and SCNN1G in the patient, and also screened for the mutation in his parents, 50 hypertensive patients and 50 controls.
RESULTS: In this patient, no mutations were found in the C-terminus of SCNN1B. However, we found a frameshift mutation caused by an 'AGCTC' deletion at the 583 codon in SCNN1G. The frameshift resulted in a new termination site at the 585 codon of the gamma-subunit and the deletion of its PY motif. Neither his parents nor 50 randomly selected patients with hypertension nor 50 controls have the mutation, indicating that this is a de novo mutation and not a common genetic polymorphism.
CONCLUSION: The de novo mutation is the first reported frameshift of the gamma-subunit causing Liddle syndrome. These data imply that a familial history of hypertension is not an essential criterion for the diagnosis of Liddle syndrome.