Université Paris Cité and Université des Antilles, INSERM, BIGR, Paris, France.
Department of Child Hematology, Reference Center for Sickle-Cell Disease Robert Debré University Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
EMBO Mol Med. 2023 Mar 8;15(3):e16320. doi: 10.15252/emmm.202216320. Epub 2023 Jan 25.
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, SLC44A2 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.
血液表型是由个体之间的遗传多态性导致红细胞（RBC）表面特定血型抗原的存在或缺失所定义的。最近基因组学和蛋白质组学方法的发展使得能够描述几个神秘的抗原。由 SLC44A2 基因编码的胆碱转运蛋白样蛋白 CTL2 在血小板聚集和中性粒细胞活化中发挥重要作用。通过研究对一种罕见血型患者中发现的高流行抗原的同种抗体，我们表明 SLC44A2 也在 RBC 中表达，并携带一个新的血型系统。此外，我们鉴定了三个同胞纯合子 SLC44A2 中的大片段缺失，导致完全 SLC44A2 缺乏。有趣的是，首次报道的 SLC44A2 缺乏个体患有进行性听力障碍、复发性动脉动脉瘤和癫痫。此外，SLC44A2 个体的血小板聚集变化不明显，也没有明显的血液系统疾病。总的来说，我们的发现证实了 SLC44A2 在听力保护中的作用，并为该蛋白在维持脑血管内稳态中的可能作用提供了新的见解。
