Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis
Hereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern European ancestry. HS is mainly associated with pathogenic variants of genes encoding defects in five membrane proteins, including anio...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/11/3/784 |
| _version_ | 1797613356182405120 |
|---|---|
| author | Dżamila M. Bogusławska Sebastian Kraszewski Michał Skulski Stanisław Potoczek Kazimierz Kuliczkowski Aleksander F. Sikorski |
| author_facet | Dżamila M. Bogusławska Sebastian Kraszewski Michał Skulski Stanisław Potoczek Kazimierz Kuliczkowski Aleksander F. Sikorski |
| author_sort | Dżamila M. Bogusławska |
| collection | DOAJ |
| description | Hereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern European ancestry. HS is mainly associated with pathogenic variants of genes encoding defects in five membrane proteins, including anion exchanger 1 encoded by the <i>SLC4A1</i> gene. In this study, in a family affected with HS, we identified a hitherto unreported AE1 defect, variant p.G720W. The result of it is most likely the HS phenotype. Molecular dynamics simulation study of the AE1 transmembrane domain may indicate reasonable changes in AE1 domain structure, i.e., significant displacement of the tryptophan residue towards the membrane surface connected with possible changes in AE1 function. The WES analysis verified by classical sequencing in conjunction with biochemical analysis and molecular simulation studies shed light on the molecular mechanism underlying this case of hereditary spherocytosis, for which the newly discovered AE1 variant p.G720W seems crucial. |
| first_indexed | 2024-03-11T06:53:42Z |
| format | Article |
| id | doaj.art-8ddca35b6b5c4f3aab5f69a8866e8c46 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:42Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8ddca35b6b5c4f3aab5f69a8866e8c462023-11-17T09:45:34ZengMDPI AGBiomedicines2227-90592023-03-0111378410.3390/biomedicines11030784Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary SpherocytosisDżamila M. Bogusławska0Sebastian Kraszewski1Michał Skulski2Stanisław Potoczek3Kazimierz Kuliczkowski4Aleksander F. Sikorski5Department of Biotechnology, Institute of Biological Sciences, University of Zielona Góra, Prof. Szafrana St. 1, 65-516 Zielona Góra, PolandDepartment of Biomedical Engineering, Wroclaw University of Science and Technology, Plac Grunwaldzki 13 (D-1), 50-377 Wroclaw, PolandDepartment of Cytobiochemistry, Faculty of Biotechnology, University of Wroclaw, F. Joliot-Curie 14a St., 50-383 Wroclaw, PolandDepartment and Clinic of Haematology, Blood Neoplasms and Bone Marrow Transplantation, Wroclaw Medical University, Wybrzeże L. Pasteura 4, 50-367 Wroclaw, PolandSilesian Park of Medical Technology Kardio-Med Silesia, ul. M. Curie-Skłodowskiej 10c, 41-800 Zabrze, PolandResearch and Development Centre, Regional Specialist Hospital, Kamieńskiego 73a, 51-154 Wroclaw, PolandHereditary spherocytosis (HS) refers to the group of the most frequently occurring non-immune hereditary hemolytic anemia in people of Caucasian central or northern European ancestry. HS is mainly associated with pathogenic variants of genes encoding defects in five membrane proteins, including anion exchanger 1 encoded by the <i>SLC4A1</i> gene. In this study, in a family affected with HS, we identified a hitherto unreported AE1 defect, variant p.G720W. The result of it is most likely the HS phenotype. Molecular dynamics simulation study of the AE1 transmembrane domain may indicate reasonable changes in AE1 domain structure, i.e., significant displacement of the tryptophan residue towards the membrane surface connected with possible changes in AE1 function. The WES analysis verified by classical sequencing in conjunction with biochemical analysis and molecular simulation studies shed light on the molecular mechanism underlying this case of hereditary spherocytosis, for which the newly discovered AE1 variant p.G720W seems crucial.https://www.mdpi.com/2227-9059/11/3/784hereditary spherocytosisanion exchanger 1erythrocyte membrane proteinmolecular dynamics simulationwhole exome sequencing |
| spellingShingle | Dżamila M. Bogusławska Sebastian Kraszewski Michał Skulski Stanisław Potoczek Kazimierz Kuliczkowski Aleksander F. Sikorski Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis Biomedicines hereditary spherocytosis anion exchanger 1 erythrocyte membrane protein molecular dynamics simulation whole exome sequencing |
| title | Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis |
| title_full | Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis |
| title_fullStr | Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis |
| title_full_unstemmed | Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis |
| title_short | Novel Variant of the <i>SLC4A1</i> Gene Associated with Hereditary Spherocytosis |
| title_sort | novel variant of the i slc4a1 i gene associated with hereditary spherocytosis |
| topic | hereditary spherocytosis anion exchanger 1 erythrocyte membrane protein molecular dynamics simulation whole exome sequencing |
| url | https://www.mdpi.com/2227-9059/11/3/784 |
| work_keys_str_mv | AT dzamilambogusławska novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis AT sebastiankraszewski novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis AT michałskulski novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis AT stanisławpotoczek novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis AT kazimierzkuliczkowski novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis AT aleksanderfsikorski novelvariantoftheislc4a1igeneassociatedwithhereditaryspherocytosis |