ArticleBlood2015
A mutation in the Gardos channel is associated with hereditary xerocytosis.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 117 citations in OpenAlex.
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- [Recurrent hemolysis and iron overload of unclear origin].Innere Medizin (Heidelberg, Germany) · 2025Article
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- Variant spectrum of PIEZO1 and KCNN4 in Japanese patients with dehydrated hereditary stomatocytosis.Human genome variation · 2023Article
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- New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration.Frontiers in physiology · 2022Article
- Red blood cell proteomics reveal remnant protein biosynthesis and folding pathways in PIEZO1-related hereditary xerocytosis.Frontiers in physiology · 2022Article
- ChanFAD: A Functional Annotation Database for Ion Channels.Frontiers in bioinformatics · 2022Article
- The Function of Ion Channels and Membrane Potential in Red Blood Cells: Toward a Systematic Analysis of the Erythroid Channelome.Frontiers in physiology · 2022Article
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- Diagnosis and clinical management of red cell membrane disorders.Hematology. American Society of Hematology. Education Program · 2021Article
- Mechanistic ion channel interactions in red cells of patients with Gárdos channelopathy.Blood advances · 2021Article
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- The EHA Research Roadmap: Anemias.HemaSphere · 2021Article
- The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance.International journal of molecular sciences · 2021Review
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20 authors at 9 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Gardos channel is a Ca(2+)-sensitive, intermediate conductance, potassium selective channel expressed in several tissues including erythrocytes and pancreas. In normal erythrocytes, it is involved in cell volume modification. Here, we report the identification of a dominantly inherited mutation in the Gardos channel in 2 unrelated families and its association with chronic hemolysis and dehydrated cells, also referred to as hereditary xerocytosis (HX). The affected individuals present chronic anemia that varies in severity. Their red cells exhibit a panel of various shape abnormalities such as elliptocytes, hemighosts, schizocytes, and very rare stomatocytic cells. The missense mutation concerns a highly conserved residue among species, located in the region interacting with Calmodulin and responsible for the channel opening and the K(+) efflux. Using 2-microelectrode experiments on Xenopus oocytes and patch-clamp electrophysiology on HEK293 cells, we demonstrated that the mutated channel exhibits a higher activity and a higher Ca(2+) sensitivity compared with the wild-type (WT) channel. The mutated channel remains sensitive to inhibition suggesting that treatment of this type of HX by a specific inhibitor of the Gardos channel could be considered. The identification of a KCNN4 mutation associated with chronic hemolysis constitutes the first report of a human disease caused by a defect of the Gardos channel.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.