Journal article
Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis)
American journal of hematology, v 90(10), pp 921-926
Oct 2015
PMID: 26178367
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant congenital hemolytic anemia with moderate splenomegaly and often compensated hemolysis. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated MCHC and MCV, and decreased osmotic fragility. The majority of symptomatic DHSt cases reported to date have been associated with gain-of-function mutations in the mechanosensitive cation channel gene, PIEZO1. A recent study has identified two families with DHSt associated with a single mutation in the KCNN4 gene encoding the Gardos channel (KCa3.1), the erythroid Ca(2+) -sensitive K(+) channel of intermediate conductance, also expressed in many other cell types. We present here, in the second report of DHSt associated with KCNN4 mutations, two previously undiagnosed DHSt families. Family NA exhibited the same de novo missense mutation as that recently described, suggesting a hot spot codon for DHSt mutations. Family WO carried a novel, inherited missense mutation in the ion transport domain of the channel. The patients' mild hemolytic anemia did not improve post-splenectomy, but splenectomy led to no serious thromboembolic events. We further characterized the expression of KCNN4 in the mutated patients and during erythroid differentiation of CD34+ cells and K562 cells. We also analyzed KCNN4 expression during mouse embryonic development.
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Details
- Title
- Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis)
- Creators
- Immacolata Andolfo - University of Naples Federico IIRoberta Russo - University of Naples Federico IIFrancesco Manna - Ceinge Biotecnologie AvanzateBoris E Shmukler - Beth Israel Deaconess Medical CenterAntonella Gambale - University of Naples Federico IIGiuseppina Vitiello - Ceinge Biotecnologie AvanzateGianluca De Rosa - University of Naples Federico IICarlo Brugnara - Boston Children's HospitalSeth L Alper - Beth Israel Deaconess Medical CenterL Michael Snyder - Quest DiagnosticsAchille Iolascon - University of Naples Federico II
- Publication Details
- American journal of hematology, v 90(10), pp 921-926
- Publisher
- Wiley
- Grant note
- R01 HL077765 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000362663900019
- Scopus ID
- 2-s2.0-84942109709
- Other Identifier
- 991022004873504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Hematology