New KCNN4 Variants Associated With Anemia: Stomatocytosis Without Erythrocyte Dehydration

The K + channel activated by the Ca 2+ , KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4 , We reported two de novo mutations on KCNN4 , V222L and H340N, chara...

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Bibliographic Details
Published in:	Frontiers in physiology Vol. 13; p. 918620
Main Authors:	Allegrini, B., Jedele, S., David Nguyen, L., Mignotet, M., Rapetti-Mauss, R., Etchebest, C., Fenneteau, O., Loubat, A., Boutet, A., Thomas, C., Durin, J., Petit, A., Badens, C., Garçon, L., Da Costa, L., Guizouarn, H.
Format:	Journal Article
Language:	English
Published:	Frontiers 08-08-2022 Frontiers Media S.A
Subjects:	Gardos Hereditary Xerocytosis KCNN4 Life Sciences Physiology red blood cell Stomatocytosis Gardos Hereditary Xerocytosis KCNN4 Stomatocytosis red blood cell
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Summary:	The K + channel activated by the Ca 2+ , KCNN4, has been shown to contribute to red blood cell dehydration in the rare hereditary hemolytic anemia, the dehydrated hereditary stomatocytosis. We report two de novo mutations on KCNN4 , We reported two de novo mutations on KCNN4 , V222L and H340N, characterized at the molecular, cellular and clinical levels. Whereas both mutations were shown to increase the calcium sensitivity of the K + channel, leading to channel opening for lower calcium concentrations compared to WT KCNN4 channel, there was no obvious red blood cell dehydration in patients carrying one or the other mutation. The clinical phenotype was greatly different between carriers of the mutated gene ranging from severe anemia for one patient to a single episode of anemia for the other patient or no documented sign of anemia for the parents who also carried the mutation. These data compared to already published KCNN4 mutations question the role of KCNN4 gain-of-function mutations in hydration status and viability of red blood cells in bloodstream.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC9393219 Reviewed by: Reinhart Reithmeier, University of Toronto, Canada This article was submitted to Red Blood Cell Physiology, a section of the journal Frontiers in Physiology John Stanley Gibson, University of Cambridge, United Kingdom Edited by: Egee Stéphane, UMR8227 Laboratoire de Biologie Intégrative des Modèles Marins, France
ISSN:	1664-042X 1664-042X
DOI:	10.3389/fphys.2022.918620