Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family

Frontiers in Pediatrics

article

Di Zhang¹  Yi Qu¹  Xue-Qi Dong¹  Yi-Ting Lu¹  Kun-Qi Yang¹  Xin-Chang Liu¹  Peng Fan¹  Yu-Xiao Hu²  Chun-Xue Yang²  Ling-Gen Gao³  Ya-Xin Liu²  Xian-Liang Zhou¹ 

[1] Department of Cardiology, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital;Emergency and Critical Care Center, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Fuwai Hospital;Department of Geriatric Cardiology, Chinese People’s Liberation Army ,(PLA) General Hospital

关键词: Liddle syndrome;    pathogenicity;    pediatrics;    amiloride-sensitive current;    longterm prognosis;   

DOI  :  10.3389/fped.2022.887214

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Objective Liddle syndrome (LS) is a monogenic hypertension consistent with autosomal dominant inheritance, often with early onset high blood pressure in childhood or adolescence. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the long-term outcomes of tailored treatment with amiloride. Methods To explore the pathogenicity of candidate variant reported in 2015 by our team, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary ( CHO ) cells using patch clamp technique. Participants were followed up for 7 years after tailored treatment with amiloride. Results A nonsense variant was detected in six members, two of whom were pediatric patients. This mutation resulted in a termination codon at codon 572, truncating the Pro-Pro-Pro-X-Tyr motif. The mutant epithelial sodium channels displayed higher amiloride-sensitive currents than the wild-type channels ( P < 0.05). Tailored treatment with amiloride achieved ideal blood pressure control in all patients with normal cardiorenal function, and no adverse events occurred during follow-up. Conclusion We found the pathogenicity of a nonsense SCNN1G mutation (p.Glu571*) with enhanced amiloride-sensitive currents in a LS family with young patients. Tailored treatment with amiloride may be an effective strategy for the long-term control of blood pressure and protection from target organ damage or cardiovascular events, including children and youth patients with LS.

【 授权许可】

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