Two Rare Mutations [CD 30 (G->C) and CDs 36/37 (−T)] in a Turkish Thalassemia Major Patient from Bulgaria

Abstract

At present, over 130 different mutations have been described causing β-thalassemia (β-thal) (1). About 20 of them account for almost 902 of the β-thal genes in the world. The others are rare mutations found in low frequencies or in single families. During our continuing studies on β-thal in Bulgaria we have found that six mutations Tcodon (CD) 39 (C->T); IVS-I-110 (G->A); IVS-I-6 (T->C); CD 5 (−CT); IVS-I-1 (6->A); IVS-II-745 (C->6)] accounted for 80% of all β-thal alleles. Eight additional mutations were observed which were present at frequencies of 0.5 to 4.8%. Of the 404 unrelated β-thal chromosomes screened for 27 different mutations, only 4% of the β-thal determinants remained unidentified (2,3). We now report the findings of two rare mutations, i.e. CD 30 (G->C) (4,5) and CDs 36/37 (−T) (6,7) in one of the uncharacterized thalassemia major patients. Both mutations appear to result in a severe β-thal due to interactions of a β->-thal allele [CDs 36/37 (−T)] with an allele that alters both β-globin pre-mRNA splicing and the structure of the hemoglobin (Hb) product [Hb Kairouan or Hb Monroe or β30(B12)Arg->Thr].