{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T06:12:28Z","timestamp":1784873548516,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T00:00:00Z","timestamp":1466726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81500155"],"award-info":[{"award-number":["81500155"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Project of Guangzhou City","award":["201509010009"],"award-info":[{"award-number":["201509010009"]}]},{"name":"Key Medical Disciplines and Specialties Program of Guangzhou in China"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The <jats:italic>RHCE<\/jats:italic> allele is highly polymorphic; more than 60 variants have been described leading to diminished expression of C, c, E, and e antigens. Not much is known about the prevalence of <jats:italic>RHCE<\/jats:italic> variants in the Chinese population. Individuals carrying a variant are at risk to develop alloantibodies in response to mismatched pregnancy or transfusion. In this study, phenotyping and genotyping of the <jats:italic>RHCE<\/jats:italic> allele in Chinese donors revealed a new clinically relevant mutation.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Blood samples from 200 D\u2013 and 200 D+ Chinese donors were analyzed by the <jats:italic>RH<\/jats:italic> multiplex ligation\u2013dependent probe amplification (MLPA) assay and compared to serologically typed RhCE phenotypes, when available. All exons of the <jats:italic>RHCE<\/jats:italic> gene were sequenced in samples with aberrant genotyping results. The phenotype of the new variant <jats:italic>RHCE<\/jats:italic> allele was tested by transducing cultured human erythroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Aberrant copy numbers for Exon 2 of the <jats:italic>RHCE<\/jats:italic> gene were discovered by MLPA in six D\u2013 donors (6\/200), but not in D+ donors (0\/200). Sequencing of the <jats:italic>RHCE<\/jats:italic> gene in these six donors identified a new variant <jats:italic>RHCE*ce308C&gt;T<\/jats:italic> (p.103Pro&gt;Leu) allele with an allele frequency of 0.015 within the D\u2013 individuals in this study. This variant was not detected in D+ individuals showing linkage with the D\u2013 haplotype. Serologically weak C expression and loss of c expression was demonstrated on donor red blood cells. In vitro transfection studies of the <jats:italic>RHCE*ce308T<\/jats:italic> variant in cDe\/ce and CDe\/CDe erythroblasts confirmed that the variant is associated with anti\u2010C reactivity while abolishing c expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Genotyping of individuals carrying this variant by standard <jats:italic>RHCE<\/jats:italic> genotyping might falsely predict a C\u2013 phenotype or a c+ phenotype. This new variant should be taken into account in <jats:italic>RHCE<\/jats:italic> genotyping assays designed for the Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.13709","type":"journal-article","created":{"date-parts":[[2016,6,25]],"date-time":"2016-06-25T18:14:24Z","timestamp":1466878464000},"page":"2314-2321","source":"Crossref","is-referenced-by-count":5,"title":["Identification of a novel frequent <i>RHCE*ce308T<\/i> variant allele in Chinese D\u2013 individuals, resulting in a C+c\u2013 phenotype"],"prefix":"10.1111","volume":"56","author":[{"given":"Tamara C.","family":"Stegmann","sequence":"first","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Centre, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center Guangzhou China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renate","family":"Bijman","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Centre, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center Guangzhou China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhi","family":"Wen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center Guangzhou China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center Guangzhou China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbera","family":"Veldhuisen","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Centre, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonneke","family":"Haer\u2010Wigman","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory Academic Medical Centre, University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Lighthart","sequence":"additional","affiliation":[{"name":"MRC\u2010Holland b.v Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lod\u00e9n\u2010van Straaten","sequence":"additional","affiliation":[{"name":"Sanquin Diagnostic Services Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center Guangzhou China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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