A novel frameshift mutation of epithelial sodium channel β‐subunit leads to Liddle syndrome in an isolated case

Summary Objective Liddle syndrome, an autosomal dominant form of monogenic hypertension, is attributed to mutations in the genes encoding β and γ subunits ( SCNN 1B and SCNN 1G ) of the epithelial sodium channel ( EN aC). The aim of this study was to search for pathogenic mutations of SCNN 1B and SCNN 1G in an adolescent under the impression of Liddle syndrome and no family history of hypertension. Design and Patients We screened the C‐terminus of SCNN 1B and SCNN 1G in an adolescent with poorly controlled hypertension who was clinically diagnosed as having Liddle syndrome. We also screened for the mutation in his parents, 100 hypertensive patients and 100 controls. Results Genetic analysis of SCNN 1B revealed a frameshift mutation induced by insertion of an additional cytosine into a string of six located between codons 617 and 618, which is predicted to introduce a new termination codon at position 621 and produce a protein truncated by 20 amino acids. This frameshift mutation was not detected in the patient's parents, the 100 hypertensive patients or the 100 controls, indicating that this is a de novo mutation and not a common genetic polymorphism. There was no mutation of SCNN 1G in any of the individuals examined. Conclusion Based on direct DNA sequencing, we identified a novel frameshift mutation in the β EN aC gene in an isolated case of Liddle syndrome. Confirmation of the diagnosis and effective tailored treatment in the patient were achieved, implying that genetic testing is a useful tool to diagnose Liddle syndrome.