Background: Liddle syndrome is a form of monogenic hypertension caused by mutations in the three homologous subunits of the epithelial sodium channels (ENaCs), α, β, and γ. It is characterized by early-onset refractory hypertension, hypokalemia, low renin activity, and hypoaldosteronism. In this study, we report a novel frame-shift mutation in responsible for Liddle syndrome in a Chinese family.
Methods: DNA samples were collected from all participants. Whole-exome sequencing was performed in the proband to detect possible causative variants. Sanger sequencing was then conducted in the other family members to verify the candidate variant, and in 100 patients with hypertension and 100 normotensive controls to exclude population genetic polymorphism.
Results: We identified a novel frame-shift mutation (c.1691_1693delinsG) in that was responsible for Liddle syndrome in this family. This mutation leads to the substitution of Arg in place of Gln at codon site 564 and generates a new stop codon at 592, influencing the crucial PY motif and resulting in reduced inactivation of the ENaCs. Aside from the proband, eight family members carried the mutation. Intra-familial phenotypic heterogeneity was observed in the blood pressure and serum potassium levels. Amiloride therapy combined with a low sodium diet is effective to alleviate the symptoms of patients with Liddle syndrome.
Conclusion: c.1691_1693delinsG, a novel frame-shift mutation in the β subunit of ENaC, was identified in a Chinese family with Liddle syndrome by whole-exome sequencing. Phenotypic heterogeneity can make diagnosis of Liddle syndrome difficult on the basis of clinical or biochemical characteristics alone. Genetic analysis is a useful tool allowing timely and accurate diagnosis of Liddle syndrome and playing a guiding role in precise treatment of the disease.
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http://dx.doi.org/10.3389/fcvm.2022.896564 | DOI Listing |
Endocr J
November 2024
Department of Pediatrics, Kagoshima University Hospital, Kagoshima 890-8520, Japan.
Liddle syndrome (LS) is an autosomal dominant genetic disorder characterized by early onset hypertension, hypokalemia, and low plasma aldosterone or renin concentration. It is caused by mutations in subunits of the epithelial sodium channel (ENaC). The clinical phenotypes of LS are variable and nonspecific, making it prone to both misdiagnosis and missed diagnosis.
View Article and Find Full Text PDFHypertension
November 2024
Department of Nephrology, INSERM EnVI U1096, CHU Rouen, CIC-CRB 1404 (D.G.), University of Rouen Normandy, France.
We describe a 17-year-old woman diagnosed with severe hypertension during routine follow-up after the prescription of a combined oral contraceptive pill. Initially, due to her age, the estradiol-containing contraception, and high-level sport practice, physicians suspected drug-induced hypertension. Blood tests showed hypokalemia, and further investigations revealed pseudoaldosteronism.
View Article and Find Full Text PDFDrug Metab Dispos
November 2024
Department of Pharmacognosy, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-Dori, Mizuho-ku, Nagoya, Japan (R.S., K.I., Y.T., T.M.); Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan (T.Y., K.F., K.W.); Department of Japanese Oriental (Kampo) Medicine, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Japan (T.N.); Department of Japanese Traditional (Kampo) Medicine, Kanazawa University Hospital, 13-1 Takaramachi, Kanazawa-City, Ishikawa, Japan (K.O.-O.); Kampo Clinical Center, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, Japan (K.O.-O.); Department of Oriental Medicine, Kameda Medical Center, 929 Higashi-cho, Kamogawa, Chiba, Japan (K.M.); Division of Pulmonary Medicine, Department of Medicine, Keio University School of Medicine, Tokyo, Japan (K.F.)
Int J Mol Sci
August 2024
Department of Nephrology, Ghent University Hospital, 9000 Ghent, Belgium.
Chronic kidney disease (CKD) is characterized by a steady decline in kidney function and affects roughly 10% of the world's population. This review focuses on the critical function of cyclic adenosine monophosphate (cAMP) signaling in CKD, specifically how it influences both protective and pathogenic processes in the kidney. cAMP, a critical secondary messenger, controls a variety of cellular functions, including transcription, metabolism, mitochondrial homeostasis, cell proliferation, and apoptosis.
View Article and Find Full Text PDFKidney Blood Press Res
October 2024
Department of Endocrinology and Metabolism, The Second People's Hospital of Guiyang, Guiyang, China.
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