Two new Cases of Heterozygosity for Hemoglobin Knossos α₂β₂ 27 Ala à Ser Detected in the French West Indies and Algeria

Abstract

Hb Knossos α₂β 27 AlaàSer was first described in a Greek family as a silent β⁺ thalassemia variant, Re-examination of 5,000 isoelectric focusing patterns of patients with rnicrocytosis allowed the presumptive identification of two additional propositi. The first originated in the French West Indies (Martinique) and the second in Algeria. A branch of the family of the second propositus was also investigated. Identification of Hb Knossos was made easily in the first family since one member was a double heterozygote for Hb S and Hb Knossos, In the second family HPLC elution of the peptide fraqments obtained by tryptic digestion of the aminoethylated β chain allowed the isolation and characterization of an abnormal βT3 peak with expected β27 Ala à Ser substitution. The Hb Knossos heterozygote from Martinique, besides an elevated α/β3 globin chain ratio, had an elevated Hb A₂ concentration in contrast to the Greek and Algerian families in which it was normal. This difference in phenotypes may be explained by the occurrence in the Mediterranean cases of a δ gene abnormality, presumably δ^o thalassemia, in position cis to the abnormal β-globin gene.