A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis
| Autor: | Pietro Izzo, Rosa Anna Avvisati, Maria Rosaria Esposito, Franck Borgese, Carmelo Piscopo, Andrea Biondani, Achille Iolascon, Luigia De Falco, Lucia De Franceschi, Hélène Guizouarn, Antonella Pantaleo |
|---|---|
| Přispěvatelé: | Institute of Developmental Biology and Cancer (IBDC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), University of Turin, Iolascon, Achille, De Falco, L., Borgese, F., Esposito, M. R., Avvisati, R. A., Izzo, P., Piscopo, C., Guizouarn, H., Biondani, A., Pantaleo, A., De Franceschi, L. |
| Rok vydání: | 2009 |
| Předmět: |
Male
Erythrocytes Xenopus membrane-protein MESH: Amino Acid Sequence skate erythrocytes anion exchanger expansion 0302 clinical medicine Anion Exchange Protein 1 Erythrocyte MESH: Xenopus MESH: Animals stomatocytosis anion exchanger dyserythropoiesis tyrosine phosphorylation Src family kinase [SDV.BDD]Life Sciences [q-bio]/Development Biology cell-volume Anemia Dyserythropoietic Congenital 0303 health sciences phosphorylation Overhydrated hereditary stomatocytosis MESH: Erythrocytes MESH: Anemia Dyserythropoietic Congenital Hematology anemia MESH: Amino Acid Substitution 3. Good health Pedigree cation content medicine.anatomical_structure Biochemistry 030220 oncology & carcinogenesis Dehydrated hereditary stomatocytosis Original Article stomatocytosis red cells dyserythropoiesis tyrosine Src family kinase k/cl cotransport band-3 Female MESH: Membrane Proteins Stomatin Stomatocytosis Adult MESH: Mutation MESH: Pedigree Blotting Western Editorials and Perspectives Biology Anemia Hemolytic Congenital MESH: Oocytes 03 medical and health sciences MESH: Anemia Hemolytic Congenital medicine MESH: Blotting Western Animals Humans Amino Acid Sequence Band 3 030304 developmental biology Family Health MESH: Humans Ion Transport Membrane Proteins MESH: Adult medicine.disease Molecular biology MESH: Male MESH: Ion Transport Red blood cell Hereditary stomatocytosis Amino Acid Substitution Mutation MESH: Family Health biology.protein Oocytes MESH: Female MESH: Anion Exchange Protein 1 Erythrocyte Cation transport |
| Zdroj: | Haematologica Haematologica, Ferrata Storti Foundation, 2009, 94 (8), pp.1049-59. ⟨10.3324/haematol.2008.002873⟩ |
| ISSN: | 1592-8721 0390-6078 |
| DOI: | 10.3324/haematol.2008.002873⟩ |
| Popis: | International audience; BACKGROUND: Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia. DESIGN AND METHODS: We report a novel variant of hereditary stomatocytosis due to a de novo band 3 mutation (p. G796R-band3 CEINGE) associated with a dyserythropoietic phenotype. Band 3 genomic analysis, measurement at of hematologic parameters and red cell indices and morphological analysis of bone marrow were carried out. We then evaluated the red cell membrane permeability and ion transport systems by functional studies of the patient's erythrocytes and Xenopus oocytes transfected with mutated band 3. We analyzed the red cell membrane tyrosine phosphorylation profile and the membrane association of the tyrosine kinases Syk and Lyn from the Src-family-kinase group, since the activity of the membrane cation transport pathways is related to cyclic phosphorylation-dephosphorylation events. RESULTS: The patient showed mild hemolytic anemia with circulating stomatocytes together with signs of dyserythropoiesis. Her red cells displayed increased Na(+) content with decreased K(+)content and abnormal membrane cation transport activities. Functional characterization of band 3 CEINGE in Xenopus oocytes showed that the mutated band 3 is converted from being an anion exchanger (Cl(-), HCO(3)(-)) to being a cation pathway for Na(+) and K(+). Increased tyrosine phosphorylation of some red cell membrane proteins was observed in diseased erythrocytes. Syk and Lyn membrane association was increased in the patient's red cells compared to in normal controls, indicating perturbation of phospho-signaling pathways involved in cell volume regulation events. CONCLUSIONS: Band 3 CEINGE alters function from that of anion exchange to cation transport, affects the membrane tyrosine phosphorylation profile, in particular of band 3 and stomatin, and its presence during red cell development likely contributes to dyserythropiesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|