Correlation between genotype and clinical features of beta-thalassemia.

Thalassemias are classified on the basis of clinical severity: thalassemia major, thalassemia intermediate, thalassemia minor. Severity of clinical pr esentation of beta-thalassemia directly depends on the globin chains imbala nce, mainly on the beta-globin chain deficiency. This study was undertaken to improve our understanding of genetic factors which lead to differences b etween phenotypes of beta-thalassemia. Twenty-six patients aged 12-24 years (16 males, 10 females) were studied. None of them had additional alpha-tha lassemia but the differences in the severity of the disease were observed i n some patients. According to the genotype the patients were divided into s ix groups IVS-I-6 (T --> C)/IVS-I-6 (T --> C) (5 patients), IVS-I-110(G --> A)/IVS-I-110(G --> A) (7 patients), IVS-I-6 (T --> C)/IVS-I-110(G --> A) ( 5 patients), IVS-I-6 (T --> C)/CD39(C --> T)(9 patients). The study include s CBC, Hb F, Gamma-globin chains, DNA and globin mRNA analysis. The relativ e levels of the gamma-mRNA were the highest in the patients with the most s evere clinical condition. The ratio between total alpha- and beta-mRNA also displays these differences. This ratio was dependent on the (combination o f) mutations that were present. Furthermore, within the two groups of patie nts with compound heterozygosities [IVS-I-6 T --> C)/IVS-I-110 (G --> a), I VS-I-6 (T --> C)/CD39(C --> T)] the highest alpha/beta mRNA ratio was seen in the most seriously affected patients. The average value of 22.2 found in 4 patients with IVS-I-6 (T --> C)/CD39(C --> T) compound heterozygosities was the highest observed and twice that of the 4 patients with the same gen otype but with much milder clinical presentation. A somewhat similar observ ation was made for patients with the IVS-I-6 (T -->, C)/IVS-I-110(G --> A) genotype. Our data (relative quantities of gamma- and beta-mRNA and alpha/b eta mRNA ratio among patients with the same genotype) suggest that there ar e some other, unknown yet, factors influencing beta-globin gene expression and reducing globin chains imbalance.