{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T07:15:59Z","timestamp":1783322159147,"version":"3.54.6"},"reference-count":15,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570166"],"award-info":[{"award-number":["82570166"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transfusion Medicine"],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n The rare erythrocyte Lutheran inhibitor (In(Lu)) blood group phenotype is characterised as a Lu\n mod<\/jats:sub>\n phenotype and primarily caused by heterozygous variants in the erythroid\u2010specific Kr\u00fceppel\u2010like factor 1 (\n KLF1<\/jats:italic>\n ) gene.\n <\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n This study aimed to analyse the genetic background of the In(Lu) phenotype in the Chinese population.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Four apparent Lu\n null<\/jats:sub>\n samples were identified among 3466 Chinese blood donors using flow cytometry. These samples were typed for Lu\n a<\/jats:sup>\n and Lu\n b<\/jats:sup>\n antigens using the gel card method. Targeted next\u2010generation sequencing (NGS) was performed to identify potential variants in blood group genes and two transcription factors,\n KLF1<\/jats:italic>\n and\n GATA1<\/jats:italic>\n , which were confirmed using Sanger and clonal sequencing. Homology modelling for both wild\u2010type and mutant residues was performed using the Robetta platform, whereas changes in protein stability resulting from variants were assessed using the DynaMut web server. The functional impact of these variants was evaluated using the PolyPhen\u20102 and PROVEAN software tools.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Four samples were identified as In(Lu). Two\n KLF1<\/jats:italic>\n variants had been previously reported, while two were novel: c.1004G>A (p.G335E) and c.1067 T>G (p.L356W). Three\u2010dimensional molecular models indicated that both the p.E335 and p.W356 substitutions altered the distance to nearby amino acid sites. The p.W356 substitution also reduced ionic interactions between p.W356 and p.D352. Both variants were predicted to adversely affect protein function.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Two novel\n KLF1<\/jats:italic>\n variants, c.1004G>A (p.G335E) and c.1067 T>G (p.L356W), were detected in two Chinese donors, suggesting an association with the In(Lu) phenotype.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/tme.70100","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:49:09Z","timestamp":1783320549000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel variants of the\n \n KLF1<\/i>\n <\/scp>\n gene associated with the In(Lu) phenotype lead to alterations in protein structure"],"prefix":"10.1111","author":[{"given":"Minghao","family":"Li","sequence":"first","affiliation":[{"name":"Immunohematology Lab Shanghai Institute of Blood Transfusion, Shanghai Blood Centre Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aijing","family":"Li","sequence":"additional","affiliation":[{"name":"Immunohematology Lab Shanghai Institute of Blood Transfusion, Shanghai Blood Centre Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-7727","authenticated-orcid":false,"given":"Ziyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Immunohematology Lab Shanghai Institute of Blood Transfusion, Shanghai Blood Centre Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyi","family":"Ye","sequence":"additional","affiliation":[{"name":"Immunohematology Lab Shanghai Institute of Blood Transfusion, Shanghai Blood Centre Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"ISBT. The International Society of Blood Transfusion (ISBT).Working party for red cell immunogenetics and blood group terminology.2025https:\/\/www.isbtweb.org\/isbt-working-parties\/rcibgt.html"},{"issue":"1","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/bjh.12184","article-title":"A novel GATA1 mutation (Stop414Arg) in a family with the rare X\u2010linked blood group Lu(a\u2013b\u2013) phenotype and mild macrothrombocytic thrombocytopenia","volume":"161","author":"Singleton BK","year":"2013","journal-title":"Br J Haematol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","DOI":"10.1002\/9781118493595","volume-title":"Human Blood Groups","author":"Daniels G","year":"2013"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/MOH.0b013e328358f92e","article-title":"Blood group phenotypes resulting from mutations in erythroid transcription factors","volume":"19","author":"Singleton BK","year":"2012","journal-title":"Curr Opin Hematol"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1182\/blood-2016-01-694331","article-title":"Kr\u00fcppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants","volume":"127","author":"Perkins A","year":"2016","journal-title":"Blood"},{"key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1182\/blood-2008-03-145672","article-title":"Mutations in EKLF\/KLF1 form the molecular basis of the rare blood group in(Lu) phenotype","volume":"112","author":"Singleton BK","year":"2008","journal-title":"Blood"},{"key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1186\/s12864-024-10148-x","article-title":"Targeted next\u2010generation sequencing and long\u2010read HiFi sequencing provide novel insights into clinically significant KLF1 variants","volume":"25","author":"Ye L","year":"2024","journal-title":"BMC Genomics"},{"key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1182\/blood-2013-09-526087","article-title":"Mutations in Kr\u00fcppel\u2010like factor 1 cause transfusion\u2010dependent hemolytic anemia and persistence of embryonic globin gene expression","volume":"123","author":"Viprakasit V","year":"2014","journal-title":"Blood"},{"key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"2414","DOI":"10.1111\/trf.14926","article-title":"Investigation of the variable in(Lu) phenotype caused by KLF1 variants","volume":"58","author":"Fraser NS","year":"2018","journal-title":"Transfusion"},{"key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1182\/blood-2014-03-561779","article-title":"KLF1 mutations are relatively more common in a thalassemia endemic region and ameliorate the severity of \u03b2\u2010thalassemia","volume":"124","author":"Liu D","year":"2014","journal-title":"Blood"},{"key":"e_1_2_11_12_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-97149-y","article-title":"Novel variants in Krueppel like factor 1 that cause persistence of fetal hemoglobin in in(Lu) individuals","volume":"11","author":"Eernstman J","year":"2021","journal-title":"Sci Rep"},{"key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/bjh.17616","article-title":"Severe neonatal haemolytic anaemia caused by compound heterozygous KLF1 mutations: report of four families and literature review","volume":"194","author":"Tangsricharoen T","year":"2021","journal-title":"Br J Haematol"},{"key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.tmrv.2019.01.004","article-title":"Genetic variants within the erythroid transcription factor, KLF1, and reduction of the expression of Lutheran and other blood group antigens: review of the in(Lu) phenotype","volume":"33","author":"Fraser NS","year":"2019","journal-title":"Transfus Med Rev"},{"key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1136\/jcp-2023-208945","article-title":"Molecular and haematological characterisation of haemolytic anaemia associated with biallelic KLF1 mutations: a case series","volume":"77","author":"Singha K","year":"2024","journal-title":"J Clin Pathol"},{"key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1038\/ejhg.2014.291","article-title":"Compound heterozygosity for KLF1 mutations is associated with microcytic hypochromic anemia and increased fetal hemoglobin","volume":"23","author":"Huang J","year":"2015","journal-title":"Eur J Hum Genet"}],"container-title":["Transfusion Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tme.70100","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/tme.70100","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tme.70100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T06:49:15Z","timestamp":1783320555000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tme.70100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,5]]},"references-count":15,"alternative-id":["10.1111\/tme.70100"],"URL":"https:\/\/doi.org\/10.1111\/tme.70100","archive":["Portico"],"relation":{},"ISSN":["0958-7578","1365-3148"],"issn-type":[{"value":"0958-7578","type":"print"},{"value":"1365-3148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,5]]},"assertion":[{"value":"2025-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"tme.70100"}}