Biochemical phenotype and origin of the three most common beta-thalassemia mutations in Serbia

Summary: Molecular (DNA) characterization of thalassemia is the most reliable methodology for the diagnosis of this group of diseases. As thalassemias are very heterogeneous, hematological data and additional biochemical analysis are essential for their differential diagnosis. In this paper we present hematological and biochemical characteristics of the carriers of three most common beta-thalassemia mutations in Serbia (Hb Lepore, b°39 and b + IVS-I-110), to be taken into consideration as the initial step of the diagnostic approach to the thalassemia patients. Also, this paper represents a detailed survey of the diversity of b-globin gene haplotypes in carriers of the most common b-thalassemia mutations and normal betaA/betaA individuals of Serbian descent. A novel haplotype associated with Hb Lepore-Boston-Washington gene has been identified in Serbian population. These data support the hypothesis of multicentric origin of this mutation. The mutation has arised de novo in the chromosomal background characteristic for Serbian population. Additionally, we have shown that two most common Mediterranean mutations, b°39 and b + IVS-I-110, have probably been introduced into Serbian population from Italy and Turkey, respectively, through historically documented migrations and settlements.