Identification of novel silent KEL alleles causing KEL:-5 (Ko) phenotype or discordance between KEL: 1,-2 phenotype/KEL *01/02 genotype

摘要

BACKGROUND: The Kell system, encoded by the KEL gene, is one of the most clinically important blood group systems. Molecular defects may lead to the absence of Kell antigen expression. The very rare KEL5 results from silent KEL genes, also called KELnull alleles. In a few cases, the rare KEL: 1,-2 phenotype may be associated with silent KEL *02 alleles. STUDY DESIGN AND METHODS: The aim of this study was to perform DNA investigations to identify silent KEL alleles among 10 KEL-5 patients and 121 individuals presenting the rare KEL: 1,-2 phenotype. Serologic investigations were performed on patients' red blood cells and serum. The KEL gene analysis was done by using a BeadChip assay (HEA Version, 1.2, Immucor), real-time polymerase chain reaction, and/or sequencing of all 19 exons of the KEL gene. RESULTS: In KEL-5 patients, two novel KELnuW alleles were described: 821 G>A being the second described KELnull allele on a KEL*01 backbone and 184Tdel. In the 121 KEL1 -2 individuals, nine (7.4%) were found to display a discordant KEL:1,-2 phenotype and KEL*01/KEL*02 genotype. Three novel silent KEL *02 alleles were described: 1084C>A, 1708G>A, and IVS11+5g>a. CONCLUSION: The number of silent KEL alleles and the notion that KEL null alleles are on a KEL*02 background may evolve in the coming years. Systematic DNA analysis showed that the number of discordant phenotype/genotype results, related to silent KEL*02 alleles was higher than expected in France. These data emphasize that clinical practice based on DNA analysis for blood group antigens requires caution and should improve the performance of the blood group phenotype prediction.