The p.R168Q mutation is associated with the Bw phenotype and a predicted decrease in the stability of the resulting...

Area of Science:

• Genetics
• Biochemistry
• Immunology

Background:

• ABO glycosyltransferase (GT) mutations can alter protein stability, leading to weak ABO phenotypes.
• The Bw phenotype is associated with specific ABO*Bw alleles and requires explanation through molecular mechanisms.

Purpose of the Study:

• To investigate the molecular basis of a novel ABO*Bw allele.
• To explain the reduced ABO antigen expression in the Bw phenotype using protein stability analysis.

Main Methods:

• ABO serology and genotyping were performed on a family.
• Three-dimensional (3D) structural analysis and protein stability change (ΔΔG) calculations were conducted for wild-type and mutant GTB enzymes.
• Flow cytometry assessed ABO antigen expression on transfected HeLa cells.

Main Results:

• A novel ABO*Bw allele (c.503G>A, p.R168Q) was identified.
• 3D homology modeling predicted reduced protein stability for the mutant GTB.
• ΔΔG values correlated inversely with ABO antigen expression, explaining the reduced expression.

Conclusions:

• Predicted protein stability changes in mutant GT enzymes can quantitatively explain reduced ABO antigen expression.
• This approach offers a convenient method for objectively assessing ABO variations.