An AQP1 allele associated with co(a-b-) phenotype

Area of Science:

• Immunogenetics
• Molecular Biology
• Blood Group Systems

Background:

• The Colton (CO) blood group system comprises four antigens (Co(a), Co(b), Co3, Co4) on aquaporin-1 (AQP1).
• The Co(a) antigen is highly prevalent (99.8%), making the Colton null phenotype (Co(a-b-)) extremely rare.
• Previous reports documented only six Co(a-b-) individuals and four silencing alleles.

Observation:

• A novel aquaporin-1 (AQP1) null allele was identified in a white female presenting with anti-Co3 antibodies.
• The identified mutation, a G deletion at nucleotide 601 (nt601delG), causes a frameshift and premature stop codon (Val201Stop) in the AQP1 gene.
• Family members were subsequently tested for the presence of this specific allele.

Findings:

• The identified nt601delG mutation in AQP1 represents a newly characterized cause of the Colton null phenotype.
• Despite the presence of anti-Co3 antibodies, which can cause hemolytic disease, the antibody was not clinically significant in this case.
• All four newborns delivered by the proband were asymptomatic, with only moderate to weakly positive direct antiglobulin tests.

Implications:

• This discovery expands the known genetic basis of the Colton null phenotype and AQP1 variations.
• The case highlights that anti-Co3 antibodies, while potentially serious, may not always result in severe clinical outcomes.
• Further research into AQP1 mutations and their clinical significance in transfusion medicine and pregnancy is warranted.