The M142T mutation causes B3 phenotype: three cases and an in vitro expression study

Area of Science:

• Genetics
• Immunology
• Molecular Biology

Background:

• The B3 phenotype, a common B subtype in Korea, is associated with the B305 allele (425 T>C, M142T).
• This allele was previously identified in Chinese individuals but not yet reported in Koreans.
• The functional impact of the M142T mutation on B3 phenotype expression remained unstudied.

Observation:

• An ABO discrepancy in a Korean family, involving a neonate, mother, and maternal aunt, led to ABO gene analysis.
• The B305 allele was detected in the neonate, mother, and maternal aunt, while the father carried the O01/O02 genotype.
• Transient transfection experiments in HeLa cells showed the B305 allele expressed 35.5% of B antigen compared to the B101 allele.

Findings:

• The M142T (425 T>C) mutation within the B305 allele is definitively linked to the B3 subtype phenotype.
• Expression levels of B antigen were quantified, with B305 showing significantly lower expression (35.5%) than the B101 allele.
• Bx01 allele transfects exhibited even lower B antigen expression (11.4%), providing a comparative benchmark.

Implications:

• This research identifies the genetic basis of the B3 subtype in the Korean population.
• Understanding the M142T mutation's effect on B antigen expression is crucial for resolving blood group discrepancies.
• The findings contribute to a deeper understanding of ABO blood group genetics and their clinical relevance.