PDF(Pubmed)
Abstract：
The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+,K+-ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness.
A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants.
We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents.
Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
A candidate gene approach and whole-exome sequencing determined the underlying genetic defect in eight patients with a novel disease phenotype comprising a hypokalemic tubulopathy with renal salt wasting, disturbed acid-base homeostasis, and sensorineural deafness. Electrophysiologic studies and surface expression experiments investigated the functional consequences of newly identified gene variants.
We identified mutations in the KCNJ16 gene encoding KCNJ16, which along with KCNJ15 and KCNJ10, constitutes the major basolateral potassium channel of the proximal and distal tubules, respectively. Coexpression of mutant KCNJ16 together with KCNJ15 or KCNJ10 in Xenopus oocytes significantly reduced currents.
Biallelic variants in KCNJ16 were identified in patients with a novel disease phenotype comprising a variable proximal and distal tubulopathy associated with deafness. Variants affect the function of heteromeric potassium channels, disturbing proximal tubular bicarbonate handling as well as distal tubular salt reabsorption.
摘要：
电解质的跨上皮运输，溶质,肾脏中的水是一个精心策划的过程，涉及许多膜转运系统。肾小管细胞中的基底外侧钾通道不仅介导钾再循环以获得适当的Na+，K+-ATP酶功能，但也参与钾和pH传感。KCNJ10基因缺陷导致EAST/SeSAME综合征,以肾脏盐消耗与癫痫相关的低钾性碱中毒为特征，共济失调,和感觉神经性耳聋.
候选基因方法和全外显子组测序确定了8名具有新疾病表型的患者的潜在遗传缺陷，这些疾病表型包括低钾性肾小管病伴有肾盐消耗，酸碱稳态受干扰，和感觉神经性耳聋.电生理研究和表面表达实验研究了新鉴定的基因变体的功能后果。
我们鉴定了编码KCNJ16的KCNJ16基因中的突变，该基因与KCNJ15和KCNJ10一起构成了近端和远端小管的主要基底外侧钾通道，分别。突变体KCNJ16与KCNJ15或KCNJ10在非洲爪狼卵母细胞中的共表达显着降低了电流。
KCNJ16的双等位基因变异在具有新疾病表型的患者中被发现，该表型包括与耳聋相关的可变近端和远端肾小管病。变体影响异聚钾通道的功能，干扰近端管状碳酸氢盐处理以及远端管状盐重吸收。
候选基因方法和全外显子组测序确定了8名具有新疾病表型的患者的潜在遗传缺陷，这些疾病表型包括低钾性肾小管病伴有肾盐消耗，酸碱稳态受干扰，和感觉神经性耳聋.电生理研究和表面表达实验研究了新鉴定的基因变体的功能后果。
我们鉴定了编码KCNJ16的KCNJ16基因中的突变，该基因与KCNJ15和KCNJ10一起构成了近端和远端小管的主要基底外侧钾通道，分别。突变体KCNJ16与KCNJ15或KCNJ10在非洲爪狼卵母细胞中的共表达显着降低了电流。
KCNJ16的双等位基因变异在具有新疾病表型的患者中被发现，该表型包括与耳聋相关的可变近端和远端肾小管病。变体影响异聚钾通道的功能，干扰近端管状碳酸氢盐处理以及远端管状盐重吸收。
