Gardos 通道病：新型 KCNN4 变异体的功能分析。
Gardos channelopathy: functional analysis of a novel KCNN4 variant.
机构信息
Unità Operativa Semplice (UOS) Fisiopatologia delle Anemie, Unità Operativa Complessa (UOC) Ematologia, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Sorbonne Université, CNRS, Integrative Biology of Marine Models, Station Biologique de Roscoff, Roscoff Cedex, France.
出版信息
Blood Adv. 2020 Dec 22;4(24):6336-6341. doi: 10.1182/bloodadvances.2020003285.
Abstract
We show that the novel variant p.S314P is a gain-of-function mutation but is less severe than the previously reported p.R352H variant. The clinical heterogeneity, blurred symptoms, and absence of specific diagnostic markers make the diagnosis of Gardos channelopathy challenging.
摘要
我们表明，新型突变 p.S314P 是一种获得性功能突变，但比先前报道的 p.R352H 变体的严重程度要低。Gardos 通道病的临床表现存在异质性，症状模糊，且缺乏特异性诊断标志物，这使得该病的诊断具有挑战性。
相似文献
1
Gardos channelopathy: functional analysis of a novel KCNN4 variant.Gardos 通道病：新型 KCNN4 变异体的功能分析。
Blood Adv. 2020 Dec 22;4(24):6336-6341. doi: 10.1182/bloodadvances.2020003285.
2
Multiple thrombosis in a patient with Gardos channelopathy and a new KCNN4 mutation.一名患有加尔多斯通道病且存在新的KCNN4突变的患者出现多处血栓形成。
Am J Hematol. 2021 Sep 1;96(9):E318-E321. doi: 10.1002/ajh.26245. Epub 2021 Jun 2.
3
'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex molecular regulation.“Gardos 通道病”：一种具有复杂分子调控的遗传性口形红细胞增多症的变异型。
Sci Rep. 2017 May 11;7(1):1744. doi: 10.1038/s41598-017-01591-w.
4
Clinical and biological features in -hereditary xerocytosis and Gardos channelopathy: a retrospective series of 126 patients.遗传性非球形细胞溶血性贫血和 Gardos 通道病的临床和生物学特征：回顾性系列 126 例患者。
Haematologica. 2019 Aug;104(8):1554-1564. doi: 10.3324/haematol.2018.205328. Epub 2019 Jan 17.
5
Severe hemolytic anemia in a newborn: Look out for rare Gardos channelopathies due to KCNN4 mutation.新生儿严重溶血性贫血：警惕因KCNN4突变导致的罕见加尔东通道病。
Pediatr Blood Cancer. 2023 Aug;70(8):e30325. doi: 10.1002/pbc.30325. Epub 2023 May 2.
6
Erythrocyte ion content and dehydration modulate maximal Gardos channel activity in KCNN4 V282M/+ hereditary xerocytosis red cells.红细胞离子含量和脱水调节 KCNN4 V282M/+遗传性非球形细胞增多症红细胞中最大 Gardos 通道活性。
Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C287-C302. doi: 10.1152/ajpcell.00074.2019. Epub 2019 May 15.
7
Rapid Gardos Hereditary Xerocytosis Diagnosis in 8 Families Using Reticulocyte Indices.利用网织红细胞指数对8个家系进行快速的加尔多斯遗传性口形细胞增多症诊断
Front Physiol. 2021 Jan 14;11:602109. doi: 10.3389/fphys.2020.602109. eCollection 2020.
8
A mutation in the Gardos channel is associated with hereditary xerocytosis.Gardos 通道突变与遗传性血影红细胞增多症有关。
Blood. 2015 Sep 10;126(11):1273-80. doi: 10.1182/blood-2015-04-642496. Epub 2015 Jul 6.
9
Erythrocytes from hereditary xerocytosis patients heterozygous for KCNN4 V282M exhibit increased spontaneous Gardos channel-like activity inhibited by senicapoc.对于KCNN4 V282M杂合的遗传性口形红细胞增多症患者，其红细胞表现出自发性加尔多斯通道样活性增加，且该活性受到司尼可泊抑制。
Am J Hematol. 2017 Jun;92(6):E108-E110. doi: 10.1002/ajh.24716. Epub 2017 Apr 29.
10
A novel channelopathy in pulmonary arterial hypertension.肺动脉高压中的一种新型通道病。
N Engl J Med. 2013 Nov 28;369(22):2161. doi: 10.1056/NEJMc1311060.
引用本文的文献
1
Design and structural basis of selective 1,4-dihydropyridine inhibitors of the calcium-activated potassium channel K3.1.钙激活钾通道K3.1的选择性1,4-二氢吡啶抑制剂的设计与结构基础
Proc Natl Acad Sci U S A. 2025 May 6;122(18):e2425494122. doi: 10.1073/pnas.2425494122. Epub 2025 Apr 28.
2
The Gárdos Channel and Piezo1 Revisited: Comparison between Reticulocytes and Mature Red Blood Cells.再探加德纳斯通道和压电蛋白 1：网织红细胞与成熟红细胞的比较。
Int J Mol Sci. 2024 Jan 24;25(3):1416. doi: 10.3390/ijms25031416.
3
Ca-Sensitive Potassium Channels.钙敏钾通道。
Molecules. 2023 Jan 16;28(2):885. doi: 10.3390/molecules28020885.
4
Influence of storage and buffer composition on the mechanical behavior of flowing red blood cells.储存条件和缓冲液成分对流动红细胞力学行为的影响。
Biophys J. 2023 Jan 17;122(2):360-373. doi: 10.1016/j.bpj.2022.12.005. Epub 2022 Dec 6.
5
Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.血液癌症中失调的钙信号传导：潜在机制与治疗潜力
Front Oncol. 2022 Oct 18;12:1010506. doi: 10.3389/fonc.2022.1010506. eCollection 2022.
6
New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration.与贫血相关的新型KCNN4变体：无红细胞脱水的口形细胞增多症
Front Physiol. 2022 Aug 8;13:918620. doi: 10.3389/fphys.2022.918620. eCollection 2022.
7
Channelopathy of small- and intermediate-conductance Ca-activated K channels.小电导和中等电导钙激活钾通道的通道病。
Acta Pharmacol Sin. 2023 Feb;44(2):259-267. doi: 10.1038/s41401-022-00935-1. Epub 2022 Jun 17.
8
The Function of Ion Channels and Membrane Potential in Red Blood Cells: Toward a Systematic Analysis of the Erythroid Channelome.红细胞中离子通道和膜电位的功能：迈向对红细胞通道组的系统分析
Front Physiol. 2022 Feb 1;13:824478. doi: 10.3389/fphys.2022.824478. eCollection 2022.
9
Channelopathy-causing mutations in the SA/SB and HA/HB helices of K2.3 and K3.1 channels alter their apparent Ca sensitivity.K2.3 和 K3.1 通道的 SA/SB 和 HA/HB 螺旋中的通道病致病突变改变了它们的钙敏感性。
Cell Calcium. 2022 Mar;102:102538. doi: 10.1016/j.ceca.2022.102538. Epub 2022 Jan 8.
10
Altered Ca Homeostasis in Red Blood Cells of Polycythemia Vera Patients Following Disturbed Organelle Sorting during Terminal Erythropoiesis.真性红细胞增多症患者终末红细胞生成过程中细胞器分拣紊乱导致红细胞内钙稳态改变。
Cells. 2021 Dec 24;11(1):49. doi: 10.3390/cells11010049.
本文引用的文献
1
Calcium Channels and Calcium-Regulated Channels in Human Red Blood Cells.人红细胞中的钙通道和钙调节通道。
Adv Exp Med Biol. 2020;1131:625-648. doi: 10.1007/978-3-030-12457-1_25.
2
Erythrocyte ion content and dehydration modulate maximal Gardos channel activity in KCNN4 V282M/+ hereditary xerocytosis red cells.红细胞离子含量和脱水调节 KCNN4 V282M/+遗传性非球形细胞增多症红细胞中最大 Gardos 通道活性。
Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C287-C302. doi: 10.1152/ajpcell.00074.2019. Epub 2019 May 15.
3
Clinical and biological features in -hereditary xerocytosis and Gardos channelopathy: a retrospective series of 126 patients.遗传性非球形细胞溶血性贫血和 Gardos 通道病的临床和生物学特征：回顾性系列 126 例患者。
Haematologica. 2019 Aug;104(8):1554-1564. doi: 10.3324/haematol.2018.205328. Epub 2019 Jan 17.
4
Genotype-phenotype correlation and risk stratification in a cohort of 123 hereditary stomatocytosis patients.123 例遗传性口形红细胞增多症患者队列的基因型-表型相关性及风险分层。
Am J Hematol. 2018 Dec;93(12):1509-1517. doi: 10.1002/ajh.25276. Epub 2018 Oct 2.
5
Use of Laser Assisted Optical Rotational Cell Analyzer (LoRRca MaxSis) in the Diagnosis of RBC Membrane Disorders, Enzyme Defects, and Congenital Dyserythropoietic Anemias: A Monocentric Study on 202 Patients.激光辅助光学旋转细胞分析仪（LoRRca MaxSis）在红细胞膜疾病、酶缺陷及先天性红细胞生成异常性贫血诊断中的应用：一项对202例患者的单中心研究
Front Physiol. 2018 Apr 27;9:451. doi: 10.3389/fphys.2018.00451. eCollection 2018.
6
Red Blood Cell Passage of Small Capillaries Is Associated with Transient Ca-mediated Adaptations.红细胞通过小毛细血管与短暂的钙介导适应性相关。
Front Physiol. 2017 Dec 5;8:979. doi: 10.3389/fphys.2017.00979. eCollection 2017.
7
Red blood cell Gardos channel (KCNN4): the essential determinant of erythrocyte dehydration in hereditary xerocytosis.红细胞加尔多斯通道（KCNN4）：遗传性干燥细胞增多症中红细胞脱水的关键决定因素。
Haematologica. 2017 Oct;102(10):e415-e418. doi: 10.3324/haematol.2017.171389. Epub 2017 Jun 15.
8
'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex molecular regulation.“Gardos 通道病”：一种具有复杂分子调控的遗传性口形红细胞增多症的变异型。
Sci Rep. 2017 May 11;7(1):1744. doi: 10.1038/s41598-017-01591-w.
9
Red Cell Properties after Different Modes of Blood Transportation.不同血液运输方式后的红细胞特性
Front Physiol. 2016 Jul 15;7:288. doi: 10.3389/fphys.2016.00288. eCollection 2016.
10
Mutations in the Gardos channel (KCNN4) are associated with hereditary xerocytosis.加尔杜斯通道（KCNN4）的突变与遗传性口形红细胞增多症相关。
Blood. 2015 Sep 10;126(11):1281-4. doi: 10.1182/blood-2015-07-657957. Epub 2015 Jul 21.
Zotero 插件