β-Thalassemia Intermedia in Two Turkish Families is Caused by the Interaction of HB Knossos [β27(B9)ALA→SER] and of HB City of hope [β69(E13)Gly→Ser] with B°-Thalassemia

Abstract

We have studied a few members of two Turkish families, who had a β-thalassemia of the intermediate type. An abnormal hemoglobin was found in both families, which when present in association with β°-thalassemia was considered to be the primary cause for the increased severity of the disease. In the first family this variant was Hb Knossos [β27(B9)Ala→-Ser] which occurred together with the frameshift in codon #8 type of β°-thalassemia. This compound heterozygosity, observed for the first time in the Turkish population was characterized by a considerable increase in Hb F production, mainly of the ^Gγ type, as expected for a chromosome with haplotype IV. In the second family, the variant was Hb City of Hope [β69(E13)Gly→Ser] which was present in combination with an unknown type of β-thalassemia. The increase in Hb F production in the compound heterozygote was minimal. Reversed phase high performance liquid chromatography and the DNA amplification-synthetic oligonucleotide probe procedure were major tools in identifying the different abnormalities.