{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:26:37Z","timestamp":1790378797263,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Science and Technology Project of Guangzhou City","award":["201607010027"],"award-info":[{"award-number":["201607010027"]}]},{"name":"Key Medical Disciplines and Specialties Program of Guangzhou"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The molecular events resulting in a weak D phenotype include missense mutations, in\u2010frame insertion, or deletion mutations of the <jats:italic>RHD<\/jats:italic> gene and hybrid <jats:italic>RHD\u2010CE\u2010D<\/jats:italic> hybrid alleles. Mutations in genes encoding the proteins that are required for proper membrane expression of Rh proteins, such as RhAG and ankyrin 1, can lead to absent or weakened expression of Rh antigens.<\/jats:p><\/jats:sec><jats:sec><jats:title>STUDY DESIGN AND METHODS<\/jats:title><jats:p>Blood sample from a Chinese blood donor with a serological weak D phenotype was collected. RhAG antigen expression, RhD, and RhCE phenotypes were determined. Analysis of the <jats:italic>RHD<\/jats:italic> and <jats:italic>RHCE<\/jats:italic> genotypes by <jats:italic>RH<\/jats:italic> multiplex ligation\u2010dependent probe amplification (MLPA), Sanger sequencing of the <jats:italic>RHD<\/jats:italic> exons, and next\u2010generation sequencing (NGS) of the <jats:italic>RHAG<\/jats:italic> and <jats:italic>ANK1<\/jats:italic> exons were performed. Expression studies in vitro were conducted by lentivirally transducing the mutant <jats:italic>RHAG*572A<\/jats:italic> or wild\u2010type <jats:italic>RHAG<\/jats:italic>, in combination with either <jats:italic>RHD<\/jats:italic> or <jats:italic>RHCE<\/jats:italic> constructs, into HEK 293 T cells. The expression of RhAG, RhD, and RhCE antigens was analyzed by flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Serological weak D and normal C + c\u2010 E\u2013 e + phenotypes, normal <jats:italic>CCDDee<\/jats:italic> genotype determined by <jats:italic>RH<\/jats:italic>\u2010MLPA, and normal sequence of the <jats:italic>RHD<\/jats:italic> gene by Sanger sequencing were demonstrated. A homozygous variant (c.572G &gt; A, p.Arg191Gln) of the <jats:italic>RHAG<\/jats:italic> gene was revealed by NGS analysis. Normal RhAG, weak RhD, and normal RhCE antigens were detected in cells transduced with the mutant <jats:italic>RHAG*572A<\/jats:italic>, the mutant <jats:italic>RHAG*572A<\/jats:italic> and <jats:italic>RHD<\/jats:italic>, and the mutant <jats:italic>RHAG*572A<\/jats:italic> and <jats:italic>RHCE<\/jats:italic> constructs, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The homozygous presence of <jats:italic>RHAG*572A<\/jats:italic> allele results in weak D expression. It does not affect RhCE expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.14969","type":"journal-article","created":{"date-parts":[[2018,10,5]],"date-time":"2018-10-05T20:11:29Z","timestamp":1538770289000},"page":"405-411","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A variant RhAG protein encoded by the <i>RHAG*572A<\/i> allele causes serological weak D expression while maintaining normal RhCE phenotypes"],"prefix":"10.1111","volume":"59","author":[{"given":"Jizhi","family":"Wen","sequence":"first","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onno J.H.M.","family":"Verhagen","sequence":"additional","affiliation":[{"name":"Sanquin Research and Landsteiner Laboratory, Academic Medical Centre University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangshuang","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianni","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Guangdong No. 2 Provincial People's Hospital  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wei","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"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"}]},{"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"}]},{"given":"Yanli","family":"Ji","sequence":"additional","affiliation":[{"name":"Institute of Clinical Blood Transfusion, Guangzhou Blood Center  Guangzhou People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Ellen","family":"van der Schoot","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":[[2018,10,4]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"50","article-title":"The genetics of the Rhesus blood group system","volume":"5","author":"Flegel WA","year":"2007","journal-title":"Blood Transfus"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13430"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.1.385"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14757"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366176"},{"key":"e_1_2_8_7_1","unstructured":"2012 Academic Press San Diego CA ME Reid C Lomas\u2010Francis ML Olsson The blood group antigen factsbook"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0296-168"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.4.2207"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.146209"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2006.02.019"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V100.3.1038"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12887"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13219"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2011.03218.x"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.12798"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.1998.6220107.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/trf.13476"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1086\/302215"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302816200"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/vox.12554"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2012.03919.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13960"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-07-171140"},{"key":"e_1_2_8_25_1","first-page":"167A","article-title":"Identification of a mutation in the RHAG gene of Japanese with weak D phenotype [abstract SP283]","volume":"53","author":"Tsuneyama H","year":"2013","journal-title":"Transfusion"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2005.05786.x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tracli.2006.02.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1003587107"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/tme.12519"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"}],"container-title":["Transfusion"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Ftrf.14969","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.14969","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/trf.14969","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/trf.14969","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T12:13:03Z","timestamp":1694347983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/trf.14969"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,4]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1111\/trf.14969"],"URL":"https:\/\/doi.org\/10.1111\/trf.14969","archive":["Portico"],"relation":{},"ISSN":["0041-1132","1537-2995"],"issn-type":[{"value":"0041-1132","type":"print"},{"value":"1537-2995","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,4]]},"assertion":[{"value":"2018-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}