Additional molecular bases of the clinically important p blood group phenotype.

BACKGROUND: The purpose of this study was to explore the molecular basis of the p phenotype by analysis of the recently cloned 4-alpha-galactosyltransferase gene responsible for synthesis of Pk (Gb3) antigen. STUDY DESIGN AND METHODS: Forty samples from individuals of eight different nationalities were investigated by serologic methods and DNA sequencing of the Pk gene.
RESULTS: Ten different Pk-null alleles, of which 6 are novel, were encountered. The 29 Swedes were homozygous for M183K or G187D, with the former as the predominant allele. Three Israelis were homozygous for a single-nucleotide deletion at codon 219 that shifts and truncates the reading frame by 5 amino acids. Two Italians were homozygous for a triplet deletion causing F81del, while an English donor was heterozygous for F81del but also carried another allele with a combined deletion and insertion. A Pole was heterozygous for alleles with either a single-base deletion at codon 257 or a mutation causing S97L. A Norwegian person and a Japanese person were homozygous for single-base insertions causing a premature stop at codon 282 or extension of the protein by 92 residues, respectively. In 2 samples no mutations were detected.
CONCLUSION: The genetic heterogeneity underlying the p phenotype is further emphasized by this study. To date, 11 p-specific mutations have been found in 14 distinct alleles.