{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T06:14:51Z","timestamp":1788416091722,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The increasing diversity of blood donor populations has created new challenges for transfusion services worldwide. The identification of donors lacking relevant high\u2010prevalence antigens is becoming increasingly important to ensure compatible blood products for alloimmunized patients and to support the development of rare donor registries. CD36 (ISBT 045) is a glycoprotein expressed on platelets, monocytes, and erythroid precursor cells. CD36 deficiency has been reported across multiple populations and is of relevance due to its association with anti\u2010CD36 isoantibodies, which may cause platelet transfusion refractoriness and fetal\/neonatal alloimmune thrombocytopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design and Methods<\/jats:title>\n                    <jats:p>We analyzed CD36 expression in 1250 blood donors of diverse ancestry using flow cytometry. CD36\u2010negative samples underwent molecular characterization using Sanger sequencing and next\u2010generation sequencing of genomic DNA, complemented by cDNA analysis and cloning to investigate transcript\u2010level alterations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified CD36 deficiency in 27 donors (2.16%). Genomic sequencing revealed 18 distinct coding variants, including three novel variants, most in the heterozygous state. In one CD36\u2010negative donor, cDNA analysis demonstrated a 52\u2010bp deletion in exon four and complete skipping of exon 9, despite the absence of splice\u2010site variants in genomic DNA. Cloning confirmed coexistence of aberrant and wild\u2010type transcripts in this individual.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that CD36 deficiency can arise from transcript\u2010level defects in the absence of detectable coding or splice\u2010site variants. These results indicate that genomic sequencing alone may be insufficient to fully resolve CD36\u2010negative phenotypes and highlight the importance of integrating transcriptomic approaches to improve molecular diagnostics and transfusion support in increasingly diverse donor populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/trf.70385","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:30:24Z","timestamp":1788413424000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular characterization of\n                    <scp>CD36<\/scp>\n                    deficiency in blood donors of Middle Eastern and African origin reveals transcript\u2010level defects beyond genomic variants"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-2954","authenticated-orcid":false,"given":"Sarah","family":"Petermann","sequence":"first","affiliation":[{"name":"German Red Cross Blood Donation Service West  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6975-6821","authenticated-orcid":false,"given":"Inga","family":"Stellmacher","sequence":"additional","affiliation":[{"name":"German Red Cross Blood Donation Service West  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5485-2645","authenticated-orcid":false,"given":"Brigitte K.","family":"Flesch","sequence":"additional","affiliation":[{"name":"German Red Cross Blood Donation Service West  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4173-9816","authenticated-orcid":false,"given":"Tanja","family":"Rehling","sequence":"additional","affiliation":[{"name":"Department of Insect Biotechnology in Plant Protection Justus Liebig University, Giessen  Giessen Germany"},{"name":"Liebig Centre for Agroecology and Climate Impact Research, International Atomic Energy Agency Collaborating Centre Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4022-4853","authenticated-orcid":false,"given":"Irina","family":"H\u00e4cker","sequence":"additional","affiliation":[{"name":"Department of Insect Biotechnology in Plant Protection Justus Liebig University, Giessen  Giessen Germany"},{"name":"Liebig Centre for Agroecology and Climate Impact Research, International Atomic Energy Agency Collaborating Centre Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9217-394X","authenticated-orcid":false,"given":"Marc F.","family":"Schetelig","sequence":"additional","affiliation":[{"name":"Department of Insect Biotechnology in Plant Protection Justus Liebig University, Giessen  Giessen Germany"},{"name":"Liebig Centre for Agroecology and Climate Impact Research, International Atomic Energy Agency Collaborating Centre Justus Liebig University Giessen  Giessen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Carbol","sequence":"additional","affiliation":[{"name":"German Red Cross Blood Donation Service West  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lambros","family":"Kordelas","sequence":"additional","affiliation":[{"name":"German Red Cross Blood Donation Service West  Ratingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/vox.13595","article-title":"Evidence that CD36 is expressed on red blood cells and constitutes a novel blood group system of clinical importance","volume":"119","author":"Alattar AG","year":"2024","journal-title":"Vox Sang"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1182\/blood.V75.3.684.684","article-title":"Identification of the platelet\u2010specific alloantigen, Naka, on platelet membrane glycoprotein IV","volume":"75","author":"Tomiyama Y","year":"1990","journal-title":"Blood"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/35016636","article-title":"Malaria susceptibility and CD36 mutation","volume":"405","author":"Aitman TJ","year":"2000","journal-title":"Nature"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI14006","article-title":"CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism","volume":"108","author":"Febbraio M","year":"2001","journal-title":"J Clin Invest"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1093\/hmg\/ddn060","article-title":"Variants in the CD36 gene associate with the metabolic syndrome and high\u2010density lipoprotein cholesterol","volume":"17","author":"Love\u2010Gregory L","year":"2008","journal-title":"Hum Mol Genet"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/trf.14369","article-title":"Fetal\/neonatal alloimmune thrombocytopenia due to anti\u2010CD36 antibodies: antibody evaluations by CD36\u2010transfected cell lines","volume":"58","author":"Lin M","year":"2018","journal-title":"Transfusion"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1160\/TH05-05-0378","article-title":"Two sibling cases of hydrops fetalis due to alloimmune anti\u2010CD36 (Nak a) antibody","volume":"95","author":"Okajima S","year":"2006","journal-title":"Thromb Haemost"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.21307\/immunohematology-2020-028","article-title":"A case of platelet transfusion refractoriness due to anti\u2010CD36 with a successful treatment outcome","volume":"35","author":"Khatri SS","year":"2019","journal-title":"Immunohematology"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1046\/j.1537-2995.1995.35996029165.x","article-title":"Posttransfusion purpura\u2010like syndrome associated with CD36 (Naka) isoimmunization","volume":"35","author":"Bierling P","year":"1995","journal-title":"Transfusion"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1046\/j.1537-2995.2002.00176.x","article-title":"Isoimmunization against CD36 (glycoprotein IV): description of four cases of neonatal isoimmune thrombocytopenia and brief review of the literature","volume":"42","author":"Curtis BR","year":"2002","journal-title":"Transfusion"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"2683","DOI":"10.1093\/hmg\/ddp192","article-title":"Positive selection of a CD36 nonsense variant in sub\u2010Saharan Africa, but no association with severe malaria phenotypes","volume":"18","author":"Fry AE","year":"2009","journal-title":"Hum Mol Genet"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1086\/346091","article-title":"CD36 polymorphism is associated with protection from cerebral malaria","volume":"72","author":"Omi K","year":"2003","journal-title":"Am J Hum Genet"},{"key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/S0140-6736(00)04138-6","article-title":"CD36 deficiency associated with insulin resistance","volume":"357","author":"Miyaoka K","year":"2001","journal-title":"Lancet"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1182\/blood.V83.2.392.392","article-title":"Platelet glycoprotein IV (CD36) deficiency is associated with the absence (type I) or the presence (type II) of glycoprotein IV on monocytes","volume":"83","author":"Yamamoto N","year":"1994","journal-title":"Blood"},{"key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1111\/trf.16398","article-title":"Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness","volume":"61","author":"Flesch BK","year":"2021","journal-title":"Transfusion"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2199-7-8","article-title":"Alternative promoter usage of the membrane glycoprotein CD36","volume":"7","author":"Andersen M","year":"2006","journal-title":"BMC Mol Biol"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","DOI":"10.3390\/genes16060705","article-title":"Human CD36: gene regulation, protein function, and its role in atherosclerosis pathogenesis","volume":"16","author":"Rac M","year":"2025","journal-title":"Genes (Basel)"},{"key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1111\/j.1537-2995.2011.03155.x","article-title":"Genetic variation of the HNA\u20103a encoding gene","volume":"51","author":"Flesch BK","year":"2011","journal-title":"Transfusion"},{"key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1172\/JCI117749","article-title":"Molecular basis of CD36 deficiency. Evidence that a 478C\u2010\u2010>T substitution (proline90\u2010\u2010>serine) in CD36 cDNA accounts for CD36 deficiency","volume":"95","author":"Kashiwagi H","year":"1995","journal-title":"J Clin Invest"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1046\/j.1537-2995.1999.39080873.x","article-title":"CD36 deficiency is frequent and can cause platelet immunization in Africans","volume":"39","author":"Lee K","year":"1999","journal-title":"Transfusion"},{"key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/S0009-8981(02)00102-X","article-title":"Genomic heterogeneity of type II CD36 deficiency","volume":"321","author":"Imai M","year":"2002","journal-title":"Clin Chim Acta"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1101\/gad.278424.116","article-title":"Spliceosomal gene mutations in myelodysplasia: molecular links to clonal abnormalities of hematopoiesis","volume":"30","author":"Inoue D","year":"2016","journal-title":"Genes Dev"},{"key":"e_1_2_9_24_1","doi-asserted-by":"crossref","DOI":"10.1080\/09537104.2023.2176168","article-title":"Frequency and molecular basis of CD36 deficiency among platelet donors in Kunming, China","volume":"34","author":"Lyu Q","year":"2023","journal-title":"Platelets"},{"key":"e_1_2_9_25_1","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2021.647400","article-title":"Identification of deep\u2010Intronic splice mutations in a large cohort of patients with inherited retinal diseases","volume":"12","author":"Qian X","year":"2021","journal-title":"Front Genet"},{"key":"e_1_2_9_26_1","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2164-9-265","article-title":"Genome\u2010wide survey of allele\u2010specific splicing in humans","volume":"9","author":"Nembaware V","year":"2008","journal-title":"BMC Genomics"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev.biochem.72.121801.161720","article-title":"Mechanisms of alternative pre\u2010messenger RNA splicing","volume":"72","author":"Black DL","year":"2003","journal-title":"Annu Rev Biochem"},{"key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.cell.2009.02.009","article-title":"The spliceosome: design principles of a dynamic RNP machine","volume":"136","author":"Wahl MC","year":"2009","journal-title":"Cell"},{"key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"D925","DOI":"10.1093\/nar\/gkae977","article-title":"The evolution of dbSNP: 25\u2009years of impact in genomic research","volume":"53","author":"Phan L","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1186\/s12864-024-10975-y","article-title":"Targeting splicing for hematological malignancies therapy","volume":"25","author":"Szelest M","year":"2024","journal-title":"BMC Genomics"},{"key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1007\/s00018-012-0990-9","article-title":"Regulation of eukaryotic gene expression by the untranslated gene regions and other non\u2010coding elements","volume":"69","author":"Barrett LW","year":"2012","journal-title":"Cell Mol Life Sci"},{"key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1101\/sqb.2019.84.039206","article-title":"3' UTRs regulate protein functions by providing a nurturing niche during protein synthesis","volume":"84","author":"Mayr C","year":"2019","journal-title":"Cold Spring Harb Symp Quant Biol"},{"key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1111\/tme.12705","article-title":"Hydrops fetalis associated with anti\u2010CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: possible underlying mechanism","volume":"30","author":"Wu Y","year":"2020","journal-title":"Transfus Med"},{"key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.2119\/2006-00088.Rac","article-title":"Molecular basis of human CD36 gene mutations","volume":"13","author":"Rac ME","year":"2007","journal-title":"Mol Med"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.70385","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.70385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:30:34Z","timestamp":1788413434000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.70385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,2]]},"references-count":33,"alternative-id":["10.1111\/trf.70385"],"URL":"https:\/\/doi.org\/10.1111\/trf.70385","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,2]]},"assertion":[{"value":"2026-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"trf.70385"}}