Novel alleles at the Kell blood group locus that lead to Kell variant phenotype in the Dutch population

• Published in: Transfusion (Philadelphia, Pa.) Pa.), 2015-02, Vol.55 (2), p.413-421
• Main Authors: Ji, Yanli, Veldhuisen, Barbera, Ligthart, Peter, Haer-Wigman, Lonneke, Jongerius, John, Boujnan, Mohamed, Ait Soussan, Aicha, Luo, Guangping, Fu, Yongshui, van der Schoot, C. Ellen, de Haas, Masja
• Format: Article
• Language: English
• Subjects: Alleles; Blood; Exons; Female; Flow cytometry; Gene Expression Regulation - genetics; Gene Frequency; Genetic Loci; Genotype & phenotype; Humans; Kell Blood-Group System - genetics; Kell Blood-Group System - metabolism; Male; Medical research; Membrane Glycoproteins - biosynthesis; Membrane Glycoproteins - genetics; Metalloendopeptidases - biosynthesis; Metalloendopeptidases - genetics; Mutation; Netherlands
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.12838

Background Alloantibodies directed against antigens of the Kell blood group system are clinically significant. In the Netherlands, the KEL1 antigen is determined in all blood donors. In this study, after phenotyping of KEL:1‐positive donors, genotyping analysis was conducted in KEL:1,–2 donors to identify possible KEL*02 variant alleles. Study Design and Methods A total of 407 donors with the KEL:1,–2 phenotype were genotyped for the KEL*01/02 polymorphism, followed by direct sequencing of the KEL gene if the KEL*02 allele was detected. Two K0 patients were also included. Transcript analysis was conducted in two probands with the KEL*02. M05 allele defined by a synonymous mutation (G573G). Flow cytometry analysis to determine the expression of Kell antigen was performed. Results Thirty KEL:1,–2 individuals (30/407, 7.4%) with discrepant KEL*01/02 genotype were identified. Seven novel alleles were identified: KEL*02(R86Q, R281W)mod, KEL*02(L133P)null, KEL*02(436delG)null, KEL*02(F418S)null, KEL*02(R492X)null, KEL*02(L611R)null, and KEL*02(R700X)null. Nine variant alleles described before were detected: KEL*02N.06, KEL*02N.15, KEL*02N.17, KEL*02N.19, KEL*02N.21, KEL*02M.02, KEL*02M.04, KEL*02M.05, and KEL*02(Q362K)mod. A transcript lacking Exon 16 was identified in two probands with the KEL*02M.05 allele as described before. Finally, flow cytometry analysis showed a decreased total Kell expression and a relatively increased KEL1 expression in individuals with the KEL:1,2null or KEL:1,2mod phenotype, compared to KEL:1,2 controls. Conclusion In 7.4% of a group of tested KEL:1,–2 Dutch donors, a KEL*02null or KEL*02mod allele was found. A relatively increased KEL1 antigen expression in KEL:1,2null and KEL:1,2mod individuals suggest that the expression of Kell‐XK complexes depends on the availability of the XK protein.