P 1 / P 2 genotyping of known and novel null alleles in the P 1 PK and GLOB histo‐blood group systems

Background The rare but clinically important null phenotypes of the P 1 PK and GLOB blood group systems are due to alterations in A 4 GALT and B 3 GALNT 1 , respectively. A recently identified single‐nucleotide polymorphism in Exon 2a of A 4 GALT predicts the common P 1 and P 2 phenotypes but rare variants have not been tested. Study Design and Methods The aim of this study was to analyze 84 p, P 1 k , and P 2 k samples, with special emphasis on unknown alleles and the P 1 / P 2 marker. Of these, 27 samples came from individuals not previously investigated genetically and were therefore subjected to sequencing of A 4 GALT or B 3 GALNT 1 , and a subset was tested by flow cytometry. Results The P 1 / P 2 genotyping linked 20 p‐inducing mutations in A 4 GALT to P 1 or P 2 allelic background. Eight p alleles remain unlinked due to compound heterozygosity. For 23 of 25 P k samples, concordant results were observed: P 1 k samples had at least one P 1 allele while P 2 k had P 2 only. The two remaining samples typed as P 1+ and P 1+ w but were genetically P 2 / P 2 . A tendency toward higher P k antigen expression was observed on P 1 k cells compared to P 2 k . In total, six previously unknown null mutations were found and characterized in A 4 GALT while four new changes were revealed in B 3 GALNT 1.Conclusion For the first time, p alleles were shown to occur on both P 1 and P 2 allelic backgrounds. Furthermore, P 1 / P 2 genotyping predicted the P 1 k versus P 2 k phenotype in more than 90% of globoside‐deficient samples. The number of GLOB ‐null alleles was increased by 50% and several P 1 PK ‐null alleles were identified.