Hb Bleuland [α108(G15)Thr→Asn, ACC→AAC (α2)]: A New Abnormal Hemoglobin Associated with a Mild α-Thalassemia Phenotype

Abstract

We report a new structural defect of the α2-globin chain, not detectable on high performance liquid chromatography (HPLC) or electrophoresis, characterized in a 12-year-old boy of Surinamese-Hindustani origin. The child was suspected to be a carrier of α-thalassemia (thal) because of microcytic hypochromic parameters in the absence of iron depletion. Gap-polymerase chain reaction (gap-PCR) revealed only normal fragments in the proband, and the pattern of a −α4.2 (leftward) deletion in his father and sister. Direct sequencing of the α-globin genes revealed an ACC→AAC transversion at codon 108 of the α2-globin gene in the proband, in his mother and in a younger sister. The new mutation predicts a Thr →Asn amino acid substitution at the corresponding residue. Threonine, a covalent binder with an R-active OH group, situated in the G helix of the α-globin chain, is involved in α1β1 contacts. Asparagine, being an equally covalent binder but with a different R-active H2N-C=O group, could make the mutated chain less suitable for tetramer cooperation. Alternatively, an absent or reduced interaction with the α hemoglobin (Hb) stabilizing protein (AHSP) could lead to loss of α chains. Hb Bleuland is the first mutation described at codon 108 and is therefore interesting in regard to the possible effects and genetic risk. The nearest variant, Hb Suan-Dok [α109(G16)Leu →Arg, CTG→CGG (α2)] was originally observed in a Thai patient affected with Hb H, in combination with an α0-thal allele. The same Hb Suan-Dok mutation, recently described in our laboratory in a carrier of African ancestry, was also not detectable as a protein and presented with an α-thal phenotype similar to Hb Bleuland.