Molecular bases of alpha-thalassemia in Argentina

The alpha-thalassemia is one of the most common hereditary disorders worldwide. Currently, molecular diagnostics is the only available tool to achieve an accurate diagnosis. The purpose of this study was to characterize the molecular bases of these syndromes in our environment and to establish genotype-phenotype associations. Through a combination of different molecular techniques and fluorescent in situ hybridization (FISH),we were able to find alpha-thalassemic mutations in 145 of the 184 patients (78.8%) studied with hematological parameters compatible with alpha-thalassemia. Deletions of the alpha-globin genes resulted the major molecular cause of the disease, and the most frequent mutation was -alpha(3.7), found in homozygous and heterozygous genotypes. In patients with a phenotypes, other prevalent mutations were -(MED) and -(CAL/CAMP). The description of a sub-telomeric deletion in a patient with alpha-thalassemia and mental retardation was also achieved. beta-thalassemic mutations in heterozygous state were found in 7.6% of the patients, who presented alpha-thalassemic clinical features (microcytosis and Hb A(2) levels below 3.5%). Hematologic profiles for the alpha(+) and alpha(0) genotypes were established for adult and pediatric patients. Hopefully, this work will provide guidelines for the detection of possible alpha-thalassemic carriers. It also highlights the collaborative work of hematologists, the biochemical and molecular biology laboratory and genetists, in order to provide appropriate genetic counseling.