Two hemoglobin variants with an alteration of the oxygen-linked chloride binding: Hb antananarivo [alpha 1(NA1)Val -> Gly] and Hb Barbizon [beta 144(HCl)Lys -> Met]

We here report two new, clinically silent, hemoglobin variants in which the structural modification disturbs the oxygen-linked chloride binding. Hb An tananarivo [alpha 1(NA1)Val-->Gly] was found during a systematic hematologi cal study in a 24-year-old woman, who originates from Madagascar. Hb Barbiz on [beta 144 (HC1)Lys-->Met] was found in several members of a French famil y. The oxygen binding properties of Hb Barbizon were similar to those of Hb Antananarivo showing, in vitro, a decreased chloride effect as compared to Hb A. In Hb Barbizon, the replacement of lysine beta 144 by a methionine r esidue decreased from 4 to 2 the excess positive charges in the central cav ity, thus leading to a reduction of about half of the chloride effect. For Hb Antananarivo, the mechanism is unclear since there is no difference in t he number of positive charges in the central cavity but alterations are lik ely at the alpha 1 alpha 2 interface.