一例c.899G>A新突变导致A亚型的分子生物学研究OA

Objective To investigate the molecular mechanism of ABO blood type gene c.899G>A leading to the occur-rence of subtype A.Methods Serological methods were used to identify ABO blood types.Genotyping was performed using polymerase chain reaction sequence specific(PCR-SSP)kits,and Sanger sequencing was used to analyze the ABO gene ex-ons 1-7.PacBio third-generation sequencing was employed for ABO gene full-length haplotype analysis.AlphaFold3 was used to predict protein structure,and ChimeraX software was used to analyze the impact of amino acid changes caused by base mutations on protein structure.Results The patient exhibited group O of forward typing and group A of reverse typ-ing.Weak A.antigen was detected by absorption-elution test.Molecular biology detection revealed three mutation sites,c.261delG,c.297A>G,and c.899G>A.Third-generation sequencing showed that one haplotype was recombinant ABO*O.01.01 and the other haplotype was recombinant ABO*B.01-O.01.01,with c.297A>G and c.899G>A located on this re-combinant haplotype.Protein structure prediction indicated that c.899G>A resulted in premature termination codons and translation interruption of ABO blood group genes,leading to a 55 amino acid deletion at the C-terminus.Conclusion The c.899G>A mutation in the ABO gene of the patient resulted in reduced A antigen expression and an A subtype phenotype.