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Novel alleles at the K ell blood group locus that lead to K ell variant phenotype in the D utch population
Author(s) -
Ji Yanli,
Veldhuisen Barbera,
Ligthart Peter,
HaerWigman Lonneke,
Jongerius John,
Boujnan Mohamed,
Ait Soussan Aicha,
Luo Guangping,
Fu Yongshui,
Schoot C. Ellen,
Haas Masja
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12838
Subject(s) - null allele , allele , biology , genotype , genotyping , microbiology and biotechnology , locus (genetics) , population , genetics , flow cytometry , gene , medicine , environmental health
Background Alloantibodies directed against antigens of the K ell blood group system are clinically significant. In the N etherlands, the KEL 1 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 K 0 patients were also included. Transcript analysis was conducted in two probands with the KEL *02. M 05 allele defined by a synonymous mutation ( G573G ). Flow cytometry analysis to determine the expression of K ell 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(436del G )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 *02 N .06 , KEL *02 N .15 , KEL *02 N .17 , KEL *02 N .19, KEL *02 N .21, KEL *02 M .02, KEL *02 M .04, KEL *02 M .05, and KEL *02( Q362K )mod . A transcript lacking E xon 16 was identified in two probands with the KEL *02M.05 allele as described before. Finally, flow cytometry analysis showed a decreased total K ell expression and a relatively increased KEL 1 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 D utch donors, a KEL *02null or KEL *02mod allele was found. A relatively increased KEL 1 antigen expression in KEL :1,2null and KEL :1,2mod individuals suggest that the expression of K ell‐ XK complexes depends on the availability of the XK protein.