Hemoglobin Montreal: a new variant with an extended beta chain due to a
deletion of Asp, Gly, Leu at positions 73, 74, and 75, and an insertion of
Ala, Arg, Cys, Gln at the same location
D Plaseska, AJ Dimovski, JB Wilson, BB Webber, HA Hume and TH Huisman
Department of Cell and Molecular Biology, Medical College of Georgia,
Augusta 30912-2100.
The unstable hemoglobin Montreal with a deletion of three amino acid
residues (Asp, Gly, Leu) at positions 73, 74, and 75 of the beta chain and
an insertion of four residues (Ala, Arg, Cys, Gln) at the same location was
observed in a 7-year-old Canadian boy suffering from a moderate hemolytic
anemia. The introduction of an extra amino acid residue and of other
changes in the crevice where the heme group is located is the likely cause
of the instability of this hemoglobin variant. The above listed changes
were detected through analyses of tryptic peptides of the beta-Montreal
chain, sequencing of amplified DNA, and hybridization of amplified DNA with
appropriate, 32P-labeled, oligonucleotide probes. It is suggested that a
mispairing involving the AGTG sequences at codons 66 and 67 and at codons
72 and 73 of the normal beta gene caused a repetition of a 16-bp segment,
while a deletion of 10 nucleotides due to recombination or slippage
followed by a second short deletion during DNA repair resulted in the
modified sequence of the beta-Montreal gene.
Volume 77,
Issue 1,
pp. 178-181,
01/01/1991
Copyright © 1991 by The American Society of Hematology
