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Two new cases of heterozygosity for hemoglobin Knossos alpha 2 beta 2 27 Ala----Ser detected in the French West Indies and Algeria.

Hb Knossos alpha 2 beta 2 27 Ala----Ser was first described in a Greek family as a silent beta(+) thalassemia variant. Reexamination of 5,000 isoelectric focusing patterns of patients with microcytosis 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 fragments obtained by tryptic digestion of the aminoethylated beta chain allowed the isolation and characterization of an abnormal beta T3 peak with expected beta 27 Ala----Ser substitution. The Hb Knossos heterozygote from Martinique, besides an elevated alpha/beta 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 delta gene abnormality, presumably delta(0) thalassemia, in position cis to the abnormal beta-globin gene.