Background: The Colton blood group system (CO, ISBT 015) is composed of three antigens, of which Co3 (ISBT 015.003) is carried by almost all persons, except those of the extremely rare Co(a-b-) phenotype. The Colton blood group antigens are expressed by the water channel aquaporin 1 (aqp1; also known as channel-forming integral protein, CHIP-28), which is a highly conserved RBC integral membrane protein. The two most frequent alleles, CO1 and CO2, encode the antigens Co(a) and Co(b), respectively. Four null alleles have been described for the AQP1 gene to date.
Case report: An Indian woman had an alloimmune antibody to an high-frequency antigen associated with mild HDN. Her RBCs were typed Co(a--b-), and the antibody was an anti-Co3. She typed CO1-positive and CO2-negative in a new genotyping method, using PCR with sequence-specific priming, for CO1 and CO2. A method for nucleotide sequencing of the four AQP1 exons from genomic DNA was developed. The patient was shown to be homozygous for a nonfunctional allele AQP1(232delG) that also carried the CO1-specific polymorphism.
Conclusion: The kindred presented a fifth example of an AQP1 null allele, which was caused by a single nucleotide deletion leading to a shift in the reading frame beyond codon 78. A method of genotyping CO for Co(a) and Co(b) antigen phenotype prediction was presented.