Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.
Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.
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DOI：
10.3389/fped.2022.887214
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发表时间：
2022
影响因子：
2.6
通讯作者：
Zhou, Xian-Liang
中科院分区：
文献类型：
--
作者：
Zhang, Di;Qu, Yi;Dong, Xue-Qi;Lu, Yi-Ting;Yang, Kun-Qi;Liu, Xin-Chang;Fan, Peng;Hu, Yu-Xiao;Yang, Chun-Xue;Gao, Ling-Gen;Liu, Ya-Xin;Zhou, Xian-Liang
利德尔综合征(LS)是一种符合常染色体显性遗传的单基因高血压，常在儿童期或青春期早期发病。本研究旨在确定一个中国LS家系中SCNN1G无义突变的致病性以及阿米洛利个体化治疗的长期结果。为了探讨本课题组2015年报道的候选突变体的致病性，我们构建了突变型和野生型体外模型，并用膜片钳技术测定了中国仓鼠卵巢(CHO)细胞对阿米洛利的敏感电流。在使用阿米洛利进行个体化治疗后，参与者被跟踪观察了7年。在六名成员中检测到一种无意义的变异，其中两名是儿科患者。这种突变导致了密码子572的终止密码子，截断了Pro-X-Tyr基序。突变型上皮钠通道显示出比野生型通道更高的阿米洛利敏感电流(P<；0.05)。阿米洛利的个体化治疗在所有心肾功能正常的患者中实现了理想的血压控制，并且在随访期间没有发生不良事件。我们在一个有年轻患者的LS家系中发现了无意义的SCNN1G突变(p.Glu571*)的致病性，该突变具有增强的阿米洛利敏感电流。阿米洛利的量身定制治疗可能是长期控制血压和预防靶器官损害或心血管事件的有效策略，包括儿童和青少年LS患者。
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. 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. 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. 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.
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影响因子：
3
作者：
Assadi, FK;Kimura, RE;Patel, S
通讯作者：
Patel, S
影响因子：
4.9
作者：
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通讯作者：
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影响因子：
30.8
作者：
HANSSON, JH;NELSONWILLIAMS, C;LIFTON, RP
通讯作者：
LIFTON, RP
DOI：
10.1016/j.vascn.2004.08.008
发表时间：
2005-05-05
影响因子：
1.9
作者：
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通讯作者：
Shapiro, Mark S.
影响因子：
2.8
作者：
Fan, Peng;Zhang, Di;Zhou, Xian-Liang
通讯作者：
Zhou, Xian-Liang