Hemoglobin Mahidol: a new hemoglobin α-chain mutant

Abstract

A slow (less anionic) hemoglobin mutant has been detected by starch gel electrophoresis of hemoglobin from three unrelated patients in Bangkok. Dissociation of the abnormal hemoglobin with p-hydroxymercuribenzoate showed that the α-chain was the site of the mutation. The mutant α-chain was isolated by carboxymethylcellulose chromatography in 8 M urea and 0.05 M β-mercaptoethanol. Peptide maps of trypsin and cyanogen bromide cleaved α-chain indicated that the amino acid alteration of the mutant was in the peptide corresponding to residues 62–76 of the α-chain. Further cleavage of this peptide with 0.25 M acetic acid at 110 °C showed that residue 74 was changed from an aspartyl to a histidyl residue, a mutation not previously described. It is proposed that this new hemoglobin α274His β2A be called hemoglobin Mahidol after Mahidol University in Bangkok. In one of the three patients showing hemoglobin Mahidol, interaction with α-thalassemia occurs and, in this patient, hemoglobin A is totally absent, being replaced by hemoglobin Mahidol together with some hemoglobin H (β4A).

Is the Human Globin Α‐chain Locus Duplicated?

“…The only accurate and practical method of recognizing a-thalassaemia trait is the demonstration of increased amount of Hb Bart's at birth. We have found that the amounts of Hb Bart's at birth are positively correlated with the severity of a-thalassaemia (Pootrakul et al, 1967a, b;Pootrakul et al, 1970; Na-Nakorn & Wasi, 1970); the concentrations of Hb Bart's in the cord blood of roo, 25, 5 and I-2% respectively represent a-thal, homozygosity, a-thalJa-thal, , a-thal, trait and a-thal, trait. cord blood data fiom Thailand (Pootrakul et d, 1970; Na-Nakorn & Wasi, 1970) and segregation of the amounts of Hb Bart's in 3 I newborn offspring of Hb H patients (Na-Nakorn et al, 1969) support the hypothesis of two a-thalassaemia alleles at a single locus.…”

“…Additional evidence in favour of one a-locus is the absence ofHb A in a-thalassaemia/Hb Q disease and in presumably Hb G a Philadelphia homozygote (Shooter et al, 1960 (Pootrakul, 1970;Pootrakul & Dixon, 1970). It was pointed out (Wasi, 1g7oa) that the two independent a-chain loci model cannot accommodate the lack of Hb A in a-thalassaemia/Hb Q disease and that in the two linked a-chain loci model the Hb Q gene must be linked with an a-thalassaemia one in the cis position.…”

Hemoglobin Chapel Hill or α2Asp→Glyβ2

“…It is, therefore, unclear why the replacement of this residue by a glycyl residue would affect the oxygen binding properties of the hemoglobin molecule; the differences that have been observed are small but appear to indicate a slight increase in oxygen affinity. Two other variants have been observed that involve substitutions of the same aspartyl residue; these are Hb-Mahidol also known as Hb-G-Taichung and Hb-GThailand in which the substitution concerns a histidyl residue [ 19,20], and Hb-G-Pest in which the aspartyl residue is replaced by an asparaginyl residue [21]. These two variants do not exhibit significant change in their functional properties.…”