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Missense mutations outside the catalytic domain of the ABO glycosyltransferase can cause weak blood group A and B phenotypes
Author(s) -
Seltsam Axel,
Blasczyk Rainer
Publication year - 2005
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/j.1537-2995.2005.00558.x
Subject(s) - abo blood group system , missense mutation , glycosyltransferase , biology , exon , microbiology and biotechnology , phenotype , gene , plasmid , transfection , mutation , genetics
BACKGROUND: Only little is known about the impact of amino acid substitutions outside an enzyme's active site on A and B transferase activity. STUDY DESIGN AND METHODS: A panel of blood group A‐ and B‐specific plasmids containing the six known missense mutations of the coding sequence upstream of exon 6 of the ABO gene were constructed. HeLa cells were used to transfect ABO expression plasmids. RESULTS: Expression of ABO variants containing single or multiple missense mutations in HeLa cells resulted in a significant decrease in the percentage of antigen‐expressing cells (up to 29%) and in mean fluorescence intensity (MFI; up to 50%) compared to transfection with ABO * A101 or ABO * B101 . Coexpression of the respective antithetical wild‐type construct ( ABO * A101 and ABO * B101 , respectively) further reduced cell surface expression of variant ABO constructs in regard to the percentage of expressing cells (up to 53% decrease) and MFI (up to 59% decrease). CONCLUSION: Weak A and B subgroups can arise from transferases with amino acid changes in the N‐terminal domain, particularly in AB phenotypes, where normal A 1 or B 1 glycosyltransferases compete for the same substrates.