HEMATOLOGIC PHENOTYPE OF THE MUTATIONS IVS1-N6 (T-]C), IVS1-N110 (G-]A), AND CD39 (C-]T) IN CARRIERS OF BETA-THALASSEMIA IN GREECE

The hematologic phenotype was characterized in heterozygotes for three of the most common beta-thalassemia mutations in the Greek population . The study included 17 carriers of beta++ IVS1-n6 (T --> C), 21 carri ers of beta + IVS1-n110 (G --> A), and 17 carriers of beta0 CD39 (C -- > T). The 55 beta-thalassemia heterozygotes were selected from among p arents of patients on regular transfusion regimens, and the beta-thala ssemia mutation was identified by means of the polymerase chain reacti on to amplify the appropriate region of the beta-globin gene and then by allele-specific oligonucleotide hybridization. The assessment of he matologic phenotype included complete blood count and quantitation of hemoglobin HbA2 and HbF and of the globin chain biosynthesis ratio. Co mparison and statistical analysis of the hematologic parameters for th e three mutations demonstrated no consistent correlation among the thr ee mutations relative to Hb levels, hematocrit, and red cell indices, although heterozygotes for the IVS1-n6 mutation produce red blood cell s with slightly higher mean corpuscular volume; significantly lower va lues of HbA2 (mean, 3.81% +/- 0.62% with four values less than 3.60%) in IVS1-n6 heterozygotes compared with IVS1-n110 heterozygotes (mean, 4.69% +/- 0.48%) and CD39 heterozygotes (mean, 4.75% +/- 0.50%, P < 0. 001); and significantly higher HbF levels in CD39 heterozygotes (mean, 2.31% +/- 1.52%) compared with IVS1-n6 heterozygotes (mean, 0.79% +/- 0.45%, P < 0.01) and IVS1-n110 heterozygotes (mean, 1.17% +/- 0.75%, P < 0.01). With respect to the HbA2 levels, the findings are in agreem ent with previous studies in Mediterranean populations; the slightly h igher levels of HbF in CD39 heterozygotes appear to be reported for th e first time.