title: Novel alleles at the Kell blood group locus that lead to Kell variant phenotype in the Dutch population.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Ji
authors.forename: Barbera
authors.initials: B
authors.lastname: Veldhuisen
authors.forename: Peter
authors.initials: P
authors.lastname: Ligthart
authors.forename: Lonneke
authors.initials: L
authors.lastname: Haer-Wigman
authors.forename: John
authors.initials: J
authors.lastname: Jongerius
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boujnan
authors.forename: Aicha
authors.initials: A
authors.lastname: Ait Soussan
authors.forename: Guangping
authors.initials: G
authors.lastname: Luo
authors.forename: Yongshui
authors.initials: Y
authors.lastname: Fu
authors.forename: C Ellen
authors.initials: CE
authors.lastname: van der Schoot
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
mesh_terms: D000483:Alleles; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005787:Gene Frequency; D056426:Genetic Loci; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D009426:Netherlands
chemical_list: D007626:Kell Blood-Group System; D008562:Membrane Glycoproteins; C585978:KEL protein, human; D008666:Metalloendopeptidases