{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:34:02Z","timestamp":1793396042754,"version":"4.5.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T00:00:00Z","timestamp":1494460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Gardos channel is a Ca<jats:sup>2+<\/jats:sup> sensitive, K<jats:sup>+<\/jats:sup> selective channel present in several tissues including RBCs, where it is involved in cell volume regulation. Recently, mutations at two different aminoacid residues in <jats:italic>KCNN4<\/jats:italic> have been reported in patients with hereditary xerocytosis. We identified by whole exome sequencing a new family with two members affected by chronic hemolytic anemia carrying mutation R352H in the <jats:italic>KCNN4<\/jats:italic> gene. No additional mutations in genes encoding for RBCs cytoskeletal, membrane or channel proteins were detected. We performed functional studies on patients\u2019 RBCs to evaluate the effects of R352H mutation on the cellular properties and eventually on the clinical phenotype. Gardos channel hyperactivation was demonstrated in circulating erythrocytes and erythroblasts differentiated <jats:italic>ex<\/jats:italic>-<jats:italic>vivo<\/jats:italic> from peripheral CD34+ cells. Pathological alterations in the function of multiple ion transport systems were observed, suggesting the presence of compensatory effects ultimately preventing cellular dehydration in patient\u2019s RBCs; moreover, flow cytometry and confocal fluorescence live-cell imaging showed Ca<jats:sup>2+<\/jats:sup> overload in the RBCs of both patients and hypersensitivity of Ca<jats:sup>2+<\/jats:sup> uptake by RBCs to swelling. Altogether these findings suggest that the \u2018Gardos channelopathy\u2019 is a complex pathology, to some extent different from the common hereditary xerocytosis.<\/jats:p>","DOI":"10.1038\/s41598-017-01591-w","type":"journal-article","created":{"date-parts":[[2017,5,5]],"date-time":"2017-05-05T10:30:24Z","timestamp":1493980224000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["\u2018Gardos Channelopathy\u2019: a variant of hereditary Stomatocytosis with complex molecular regulation"],"prefix":"10.1038","volume":"7","author":[{"given":"Elisa","family":"Fermo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Bogdanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"Petkova-Kirova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zaninoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Paola","family":"Marcello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asya","family":"Makhro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"H\u00e4nggi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Hertz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Danielczok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Vercellati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Mirra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zanella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agostino","family":"Cortelezzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilma","family":"Barcellini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Kaestner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bianchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,11]]},"reference":[{"key":"1591_CR1","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/S1357-2725(02)00310-2","volume":"35","author":"AD Maher","year":"2003","unstructured":"Maher, A. 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