Truncated Epithelial Sodium Channel ß Subunit Responsible for Liddle Syndrome in a Chinese Family.

BACKGROUND/AIMS: Liddle syndrome (LS) is a rare autosomal dominant disease caused by mutations in genes coding for epithelial sodium channel (ENaC) subunits. The aim of this study was to identify the mutation responsible for the LS in an extended Chinese family. METHODS: DNA samples from the proband with early-onset, treatment-resistant hypertension, and hypokalemia and 19 additional relatives were all sequenced for mutations in exon 13 of the ß-ENaC and γ-ENaC genes, using amplification by polymerase chain reaction and direct DNA sequencing. RESULTS: Genetic testing of exon 13 of SCNN1B revealed duplication of guanine into a string of 3 guanines located at codon 602. This frameshift mutation is predicted to generate a premature stop codon at position 607, resulting in truncated ß-ENaC lacking the remaining 34 amino acids, including the crucial PY motif. Among a total of 9 participants with the identical mutation, different phenotypes were identified. Tailored treatment with amiloride was safe and effective in alleviating disease symptoms in LS. No mutation of SCNN1G was identified in any of the examined participants. CONCLUSIONS: We report here a family affected by LS harboring a frameshift mutation (c.1806dupG) with a premature stop codon deleting the PY motif of ß-ENaC. Our study demonstrates that the earlier LS patients are diagnosed by genetic testing and treated with tailored medication, the greater the likelihood of preventing or minimizing complications in the vasculature and target organs.

Liddle syndrome misdiagnosed as primary aldosteronism resulting from a novel frameshift mutation of SCNN1B.

Liddle syndrome (LS), a monogenetic autosomal dominant disorder, is mainly characterized by early-onset hypertension and hypokalemia. Clinically, misdiagnosis or missing diagnosis is common, since clinical phenotypes of LS are variable and nonspecific. We report a family with misdiagnosis of primary aldosteronism (PA), but identify as LS with a pathogenic frameshift mutation of the epithelial sodium channel (ENaC) ß subunit. DNA samples were collected from a 32-year-old proband and 31 other relatives in the same family. A designed panel including 41 genes associated with monogenic hypertension was screened using next-generation sequencing. The best candidate disease-causing variants were verified by Sanger sequencing. Genetic analysis of the proband revealed a novel frameshift mutation c.1838delC (p.Pro613Glnfs*675) in exon 13 of SCNN1B. This heterozygous mutation involved the deletion of a cytosine from a string of three consecutive cytosines located at codons 612 to 613 and resulted in deletion of the crucial PY motif and elongation of the ß-ENaC protein. The identical mutation was also found in 12 affected family members. Amiloride was effective in alleviating LS for patients. There were no SCNN1A or SCNN1G mutations in this family. Our study emphasizes the importance of considering LS in the differential diagnosis of early-onset hypertension. The identification of a novel frameshift mutation of SCNN1B enriches the genetic spectrum of LS and has allowed treatment of this affected family to prevent severe complications.

[Management of refractory ventricular tachycardia in patients with non-myxomas primary cardiac tumors].

OBJECTIVE: To summarize the clinical characteristics and treatment experience of patients with non-myxomas primary cardiac tumors accompanied with refractory ventricular tachycardia (VT). METHODS: Clinical and imaging data as well as therapy efficacy and outcome were analyzed in 10 patients with non-myxomas primary cardiac tumors accompanied with refractory VT. RESULTS: There were 5 male and 5 female patients in this cohort [mean age (37.6±18.2) years]. Palpitation was presented in all 10 patients, 7 patients experienced syncope, and 2 patients suffered from amaurosis. The diagnosis was made by combined use of transthoracic echocardiograms, MRI, and CT scan. The time from symptom to diagnosis was (33.2±36.7) months. Symptom-related VT was documented by ECG or Holter monitoring. MRI suggested lipoma in 7 patients, lymphoma in 1 patient and fibroma in another patient. Seven tumors were located in the left ventricle, 1 in right atria, 1 at peri-aortic root and 1 near right ventricular outflow tract. Nine out of 10 patients received anti-arrhythmic drug therapy. The ventricular tachyarrhythmia disappeared after surgical tumor resection in 4 patients. All other patients who were treated with antiarrhythmic drugs, radiofrequency ablation or subtotal excision showed only suboptimal efficacy during (39.4±25.1) months follow-up. CONCLUSION: Surgical tumor removal is the best treatment strategy for the treatment of refractory ventricular tachycardia in patients with primary cardiac benign tumors.