Double heterozygosity of the thalassemic mutations term. Cd +6 C→G and IVS-I-110 in a Greek woman: A case presentation.

The phenotypic and molecular diversity of compound heterozygosity for thalassemic genes in Greece is extensive. The interaction of silent and classic β-thalassemia results in the clinical phenotype of thalassemia intermedia. We report the clinical and hematological findings in an 18-year-old female referred to our hemoglobinopathy prevention unit that was observed to be compound heterozygote for the β-thalassemia mutations termination Cd +6 C→G and IVS-I-110. Her parents were heterozygous for 1 of the 2 thalassemia genes. Termination Cd +6 C→G in the 3’ untranslated region (3’UTR of the β-globin gene (+1480 C→G) mutation is very rare and was previously reported in only a few Greek families [1,2]. The young woman had been followed-up since childhood for anemia, prior to the definitive characterization of her β genotype. Her clinical phenotype was mild, with anemia and slight splenomegaly, but without jaundice or the need for transfusion. Her growth and development as a child were satisfactory. Hematological data of the propositus were as follows: Hb: 8.2 g/dL; Hct: 25.2%; MCV: 60.4 fL; MCH: 19.5 g/dL; RBC: 4180×103 μL. Her ferritin level was 27 ng/mL and HPLC hemoglobin variant analysis showed Ηb A2 was 6.6% and Hb F was <2%. Microscopic examination of a stained peripheral blood smear showed severe anisocytosis, microcytosis, and basophilic stippling. No erythroblasts were noted. Written informed consent was obtained from the patient. Hematological findings in the mother were as follows: Hb: 12.2 g/dL; Hct: 38.1%; MCV: 67 fL; MCH: 21 g/dL; RBC: 5690×103 μL; Ηb A2: 5%; Hb F: <2%. Her father’s hematological data were within normal limits (with the exception of an Ηb A2 level of 3.4%), as follows: Hb: 14.9 g/dL; Hct: 45.3%; MCV: 87 fL; MCH: 28.6 g/dL; RBC: 5190×103 μL Molecular examination showed that the mother carried the typical β-thalassemia mutation ΙVSI-110, which is the most common β-thalassemia mutation in the Greek population [3] and the father carried