Back to Search
Start Over
‘Gardos Channelopathy’: a variant of hereditary Stomatocytosis with complex molecular regulation
- Source :
- Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017), Fermo, Elisa; Bogdanova, Anna; Petkova-Kirova, Polina; Zaninoni, Anna; Marcello, Anna Paola; Makhro, Asya; Hänggi, Pascal; Hertz, Laura; Danielczok, Jens; Vercellati, Cristina; Mirra, Nadia; Zanella, Alberto; Cortelezzi, Agostino; Barcellini, Wilma; Kaestner, Lars; Bianchi, Paola (2017). Gardos Channelopathy: a variant of hereditary Stomatocytosis with complex molecular regulation. Scientific Rep, Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- The Gardos channel is a Ca2+ sensitive, K+ selective channel present in several tissues including RBCs, where it is involved in cell volume regulation. Recently, mutations at two different aminoacid residues in KCNN4 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 KCNN4 gene. No additional mutations in genes encoding for RBCs cytoskeletal, membrane or channel proteins were detected. We performed functional studies on patients’ 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 ex-vivo 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’s RBCs; moreover, flow cytometry and confocal fluorescence live-cell imaging showed Ca2+ overload in the RBCs of both patients and hypersensitivity of Ca2+ uptake by RBCs to swelling. Altogether these findings suggest that the ‘Gardos channelopathy’ is a complex pathology, to some extent different from the common hereditary xerocytosis.
- Subjects :
- Male
Erythrocytes
Hydrops Fetalis
Inheritance Patterns
medicine.disease_cause
Adenosine Triphosphate
0302 clinical medicine
Child
Cytoskeleton
Exome sequencing
Calcium signaling
Erythroid Precursor Cells
Mutation
Multidisciplinary
medicine.diagnostic_test
10081 Institute of Veterinary Physiology
Intermediate-Conductance Calcium-Activated Potassium Channels
Pedigree
3. Good health
Cell biology
10076 Center for Integrative Human Physiology
030220 oncology & carcinogenesis
Medicine
Female
Glycolysis
Adult
Adolescent
Science
Biology
Anemia, Hemolytic, Congenital
Models, Biological
Article
Flow cytometry
03 medical and health sciences
KCNN4
Channelopathy
medicine
Humans
Family
Calcium Signaling
1000 Multidisciplinary
Sodium
Infant
medicine.disease
Hereditary stomatocytosis
Immunology
570 Life sciences
biology
Channelopathies
030215 immunology
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....ec52fd85ac8e86e7484ac76c03118340