An AQP1 null allele in an Indian woman with Co (a-b-) phenotype and high-titer anti-Co3 associated with mild HDN

BACKGROUND: The Colton blood group system (CO, ISBT 015) is composed of thr ee 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 gro up antigens are expressed by the water channel aquaporin 1 (aqp1; also know n as channel-forming integral protein, CHIP-28), which is a highly. conserv ed RBC integral membrane protein. The two most frequent alleles, COY and CO 2, 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-frequenc y antigen associated with mild HDN. Her RBCs were typed Co(a-b-), and the a ntibody was an anti-Co3. She typed CO1-positive and CO2-negative in a new g enotyping method, using PCR with sequence-specific priming, for COY and CO2 . A method for nucleotide sequencing of the four AQP1 exons from genomic DN A 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, w hich was caused by a single nucleotide deletion leading to a shift in the r eading frame beyond codon 78. A method of genotyping CO for Co-a and Co-b a ntigen phenotype prediction was presented.