{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:00:46Z","timestamp":1790341246117,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Identification of variants causing Rh deficiency phenotypes is important to allow safe transfusions and prevent hemolytic disease of the fetus and newborn. During preoperative screening for pseudomyxoma peritonei, a patient presented with suspicion of Rh\u2010deficiency syndrome. The effect of these variants on the expression of Rh and Rh associated proteins was studied.<\/jats:p>\n <\/jats:sec>\n \n Study Design & Methods<\/jats:title>\n Serotyping, MLPA genotyping, and next\u2010generation sequencing were performed on the RBCs of the proband and their family members. The effect of the variants on membrane expression of RhAG, Rh proteins, as well as Rh complex membrane proteins was evaluated using flow cytometry and western blot. Transient transfection experiments were conducted to assay the consequences of the RhAG variants on RhAG, RhD, and RhCE membrane expression.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Two novel missense variants in\n RHAG<\/jats:italic>\n ,\n RHAG<\/jats:italic>\n :c.172C>T and\n RHAG<\/jats:italic>\n :c.242G>A were identified resulting in an Rh\n mod<\/jats:sup>\n phenotype. The novel\n RHAG<\/jats:italic>\n variants decreased RhAG expression with a concomitant reduction in expression of Rh proteins and CD47 while a slight increase in band3 expression was observed in the proband. A reduction of CD44 expression was also observed. Transfection of c.172C>T did not lead to a lower RhAG expression, while in contrast, expression of c.242G>A was significantly decreased compared to RhAGwt. Both led to a reduction of RhD and RhCE expression. Co\u2010transfection of\n RHAG<\/jats:italic>\n wt with c.172C>T or c.242G>A led to a significant reduction in RhD and RhCE expression.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Two novel\n RHAG<\/jats:italic>\n variants leading to Rh\n mod<\/jats:sup>\n phenotype were identified. A decrease in CD44 expression not previously associated with this phenotype was observed.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/trf.70366","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:15:56Z","timestamp":1790338556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel missense variants in the\n \n RHAG<\/i>\n <\/scp>\n gene that result in Rh\n mod<\/sup>\n phenotype"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6044-1592","authenticated-orcid":false,"given":"Youmna","family":"al Halabi","sequence":"first","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Ligthart","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Immunohematology Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Iacono","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbera","family":"Veldhuisen","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Immunohematology Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurcan","family":"Yagci","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Javadi","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerly","family":"Fu","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan J.","family":"Cruijsen","sequence":"additional","affiliation":[{"name":"Department of Hematology Catharina Hospital Eindhoven Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignace H. J. T.","family":"de Hingh","sequence":"additional","affiliation":[{"name":"Department of Surgery Catharina Hospital Eindhoven Eindhoven The Netherlands"},{"name":"GROW\u2014School for Oncology and Reproduction Maastricht University Maastricht Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0126-4695","authenticated-orcid":false,"given":"Daan","family":"van de Kerkhof","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Catharina Hospital Eindhoven Eindhoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu C. J.","family":"Bosman","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry, Hematology & Immunology Diakonessenhuis Hospital Utrecht the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gestur","family":"Vidarsson","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8065-3540","authenticated-orcid":false,"given":"Ellen","family":"van der Schoot","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"},{"name":"Department of Diagnostic Immunohematology Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2596-0046","authenticated-orcid":false,"given":"Emile","family":"van den Akker","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03218.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2478\/immunohematology-2025-007"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.transci.2016.12.003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.3.1038"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2478\/immunohematology-2025-002"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)07069-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.2.375"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096-8652(199909)62:1<25::aid-ajh5>3.0.co;2-k"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/302215"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.14969"},{"key":"e_1_2_8_13_1","doi-asserted-by":"crossref","unstructured":"ValleseF KimK JohnstonJD NobleAJ CaliT ClarkeOB.Architecture of the human erythrocyte ankyrin\u20101 complex. 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