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A weak blood group A phenotype caused by a translation‐initiator mutation in the ABO gene
Author(s) -
Seltsam Axel,
Das Gupta Christa,
BadeDoeding Christina,
Blasczyk Rainer
Publication year - 2006
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.1537-2995.2006.00740.x
Subject(s) - abo blood group system , allele , biology , microbiology and biotechnology , phenotype , transfection , mutation , start codon , gene , stop codon , antigen , genetics , messenger rna
BACKGROUND: Weak blood group A and B phenotypes are correlated with ABO glycosyltransferases exhibiting single‐amino‐acid changes and/or C‐terminal modifications. STUDY DESIGN AND METHODS: A healthy donor diagnosed as having weak A antigen expression and his two children were subjected to extensive ABO typing. HeLa cells were used to transfect ABO expression plasmids. RESULTS: The donor's red blood cells were type A weak B and his serum sample contained weakly reactive anti‐A 1 antibodies. A single T>C transition identified at the +2 position of the start codon of an ABO * A101 allele predicted the disruption of this methionine codon. In the transfection studies, a significant reduction of A activity was observed on HeLa cells transfected with a plasmid containing the variant ABO * A allele. Coexpression of the respective antithetical ABO * B101 wild‐type construct further reduced cell surface A antigen expression. Similar expression results were obtained with ABO constructs in which the Met 1 start codon and five alternative start sites at codons 20, 26, 43, 53, and 69 had successively been interrupted. CONCLUSION: The donor's weak blood group A phenotype most likely resulted from expression of an N‐truncated A transferase triggered by alternative translation start sites in the transmembrane domain or stem region.