Aweak phenotype associated with novel ABO*A allele variant c.106delinsGG.

Abstract

Discrepancy between forward and reverse ABO grouping could be due to several reasons including genetic mutations of the alleles encoding group specific transferase. The healthy donors found with weak A antigen were investigated to ascertain the allele responsible for variation. Standard serological methods were employed using commercial antisera. The molecular sequencing was performed on DNA with enrichment library prep kit and a custom designed overlapping probe panel. Binary alignment mapping files, generated on board the Illumina MiSeq instrument and aligned to the GRCh37/Hg19 reference genome, were uploaded to the QIAGEN CLC genomics workbench software (version. 20) where variant call files were generated and analyzed. Red blood cells (RBCs) of six healthy donors, showing weak mix-field agglutination by anti-A and anti-A, B and plasma with absence or weakly reacting anti-A, were investigated serologically. The RBCs incubated with anti-A yield positive elution and their saliva lacked A but possessed H antigen thereby classifying as a historical known phenotype Aend. Family study on 4 probands showed inheritance of the trait. Molecular studies revealed presence of ABO*A allele carrying rare novel variant referred to as c.106delinsGG in line with HGVS recommendation that was thought to be responsible for the variant of A. Six cases serologically defined as Aweak were found to be associated with novel allele ABO*A (c.106delinsGG). The Aweak phenotype with the novel allele has not been displayed on International Society of Blood Transfusion database, though c.106delinsGG is listed in the UCSC genome browser under rs782544248.