巴特综合征
氯离子通道
错义突变
遗传学
无义突变
巴特综合征
基因
生物
低钾血症
突变体
突变
细胞生物学
内分泌学
作者
Olga Andrini,Mathilde Keck,Rodolfo Briones,Stéphane Lourdel,Rosa Vargas‐Poussou,Jacques Teulon
出处
期刊:American Journal of Physiology-renal Physiology
[American Physiological Society]
日期:2015-06-15
卷期号:308 (12): F1324-F1334
被引量:49
标识
DOI:10.1152/ajprenal.00004.2015
摘要
The mutations in the CLCNKB gene encoding the ClC-Kb chloride channel are responsible for Bartter syndrome type 3, one of the four variants of Bartter syndrome in the genetically based nomenclature. All forms of Bartter syndrome are characterized by hypokalemia, metabolic alkalosis, and secondary hyperaldosteronism, but Bartter syndrome type 3 has the most heterogeneous presentation, extending from severe to very mild. A relatively large number of CLCNKB mutations have been reported, including gene deletions and nonsense or missense mutations. However, only 20 CLCNKB mutations have been functionally analyzed, due to technical difficulties regarding ClC-Kb functional expression in heterologous systems. This review provides an overview of recent progress in the functional consequences of CLCNKB mutations on ClC-Kb chloride channel activity. It has been observed that 1) all ClC-Kb mutants have an impaired expression at the membrane; and 2) a minority of the mutants combines reduced membrane expression with altered pH-dependent channel gating. Although further investigation is needed to fully characterize disease pathogenesis, Bartter syndrome type 3 probably belongs to the large family of conformational diseases, in which the mutations destabilize channel structure, inducing ClC-Kb retention in the endoplasmic reticulum and accelerated channel degradation.
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