Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype
Abstract Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens...
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-03-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202216320 |
| _version_ | 1797282931271532544 |
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| author | Bérengère Koehl Cédric Vrignaud Mahmoud Mikdar Thankam S Nair Lucy Yang Seyve Landry Guy Laiguillon Claudine Giroux‐Lathuile Sophie Anselme‐Martin Hanane El Kenz Olivier Hermine Narla Mohandas Jean Pierre Cartron Yves Colin Olivier Detante Raphaël Marlu Caroline Le Van Kim Thomas E Carey Slim Azouzi Thierry Peyrard |
| author_facet | Bérengère Koehl Cédric Vrignaud Mahmoud Mikdar Thankam S Nair Lucy Yang Seyve Landry Guy Laiguillon Claudine Giroux‐Lathuile Sophie Anselme‐Martin Hanane El Kenz Olivier Hermine Narla Mohandas Jean Pierre Cartron Yves Colin Olivier Detante Raphaël Marlu Caroline Le Van Kim Thomas E Carey Slim Azouzi Thierry Peyrard |
| author_sort | Bérengère Koehl |
| collection | DOAJ |
| description | Abstract Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens. The choline transporter‐like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil activation. By investigating alloantibodies to a high‐prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that SLC44A2 is also expressed in RBCs and carries a new blood group system. Furthermore, we identified three siblings homozygous for a large deletion in SLC44A2, resulting in complete SLC44A2 deficiency. Interestingly, the first‐ever reported SLC44A2‐deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms, and epilepsy. Furthermore, SLC44A2null individuals showed no significant platelet aggregation changes and do not suffer from any apparent hematological disorders. Overall, our findings confirm the function of SLC44A2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis. |
| first_indexed | 2024-03-07T17:21:39Z |
| format | Article |
| id | doaj.art-f2d7a59490f64da5ad7587622cbb7e66 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:21:39Z |
| publishDate | 2023-03-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-f2d7a59490f64da5ad7587622cbb7e662024-03-02T20:05:00ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-03-01153n/an/a10.15252/emmm.202216320Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotypeBérengère Koehl0Cédric Vrignaud1Mahmoud Mikdar2Thankam S Nair3Lucy Yang4Seyve Landry5Guy Laiguillon6Claudine Giroux‐Lathuile7Sophie Anselme‐Martin8Hanane El Kenz9Olivier Hermine10Narla Mohandas11Jean Pierre Cartron12Yves Colin13Olivier Detante14Raphaël Marlu15Caroline Le Van Kim16Thomas E Carey17Slim Azouzi18Thierry Peyrard19Université Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceKresge Hearing Research Institute, Department of Otolaryngology/Head and Neck Surgery University of Michigan Ann Arbor MI USAKresge Hearing Research Institute, Department of Otolaryngology/Head and Neck Surgery University of Michigan Ann Arbor MI USAHemostasis Laboratory Grenoble Alpes University Hospital Grenoble Grenoble FranceÉtablissement Français de Sang (EFS) Ile‐de‐France, Centre National de Référence pour les Groupes Sanguins Paris FranceEtablissement Français du Sang Auvergne Rhône Alpes, Immunohematology Laboratory Grenoble FranceEtablissement Français du Sang Auvergne Rhône Alpes, Immunohematology Laboratory Grenoble FranceDepartment of Transfusion, Blood Bank, CHU‐Brugmann and Hôpital Universitaire des Enfants Reine Fabiola Université Libre de Bruxelles Brussels BelgiumUniversité de Paris, Imagine Institute, INSERM UMR 1163 Paris FranceRed Cell Physiology Laboratory, New York Blood Center New York NY USAUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceStroke Unit, Neurology Department, Grenoble Hospital, Grenoble Institute of Neurosciences, Inserm U1216 University of Grenoble Alpes Grenoble FranceHemostasis Laboratory Grenoble Alpes University Hospital Grenoble Grenoble FranceUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceKresge Hearing Research Institute, Department of Otolaryngology/Head and Neck Surgery University of Michigan Ann Arbor MI USAUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceUniversité Paris Cité and Université des Antilles, INSERM, BIGR Paris FranceAbstract Blood phenotypes are defined by the presence or absence of specific blood group antigens at the red blood cell (RBC) surface, due to genetic polymorphisms among individuals. The recent development of genomic and proteomic approaches enabled the characterization of several enigmatic antigens. The choline transporter‐like protein CTL2 encoded by the SLC44A2 gene plays an important role in platelet aggregation and neutrophil activation. By investigating alloantibodies to a high‐prevalence antigen of unknown specificity, found in patients with a rare blood type, we showed that SLC44A2 is also expressed in RBCs and carries a new blood group system. Furthermore, we identified three siblings homozygous for a large deletion in SLC44A2, resulting in complete SLC44A2 deficiency. Interestingly, the first‐ever reported SLC44A2‐deficient individuals suffer from progressive hearing impairment, recurrent arterial aneurysms, and epilepsy. Furthermore, SLC44A2null individuals showed no significant platelet aggregation changes and do not suffer from any apparent hematological disorders. Overall, our findings confirm the function of SLC44A2 in hearing preservation and provide new insights into the possible role of this protein in maintaining cerebrovascular homeostasis.https://doi.org/10.15252/emmm.202216320blood group antigenhearing impairmentred blood cellsSLC44A2transfusion |
| spellingShingle | Bérengère Koehl Cédric Vrignaud Mahmoud Mikdar Thankam S Nair Lucy Yang Seyve Landry Guy Laiguillon Claudine Giroux‐Lathuile Sophie Anselme‐Martin Hanane El Kenz Olivier Hermine Narla Mohandas Jean Pierre Cartron Yves Colin Olivier Detante Raphaël Marlu Caroline Le Van Kim Thomas E Carey Slim Azouzi Thierry Peyrard Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype EMBO Molecular Medicine blood group antigen hearing impairment red blood cells SLC44A2 transfusion |
| title | Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype |
| title_full | Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype |
| title_fullStr | Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype |
| title_full_unstemmed | Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype |
| title_short | Lack of the human choline transporter‐like protein SLC44A2 causes hearing impairment and a rare red blood phenotype |
| title_sort | lack of the human choline transporter like protein slc44a2 causes hearing impairment and a rare red blood phenotype |
| topic | blood group antigen hearing impairment red blood cells SLC44A2 transfusion |
| url | https://doi.org/10.15252/emmm.202216320 |
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