β-Intermediate Thalasemia: triplication of genes α / β thalassemia heterozygous in Spain

Abstract

Objectives. Check with hematological data that the diagnosis and clinical grade of β-thalassemia intermedia can be established when a triplication of genes alpha (αααanti 3.7) and heterozygous β-thalassemia are coherent. Methods. Retrospective study in which 73 patients of Caucasian origin participated, who simultaneously showed a tripling or quadrupling of the genes α and heterozygous β-thalassemia. Screening for the most frequent α-thalassemia mutations, as well as gene triplication (αααanti 3.7) was carried out by multiplex PCR followed by reverse hybridization and confirmed by MLPA. The molecular diagnosis of β-thalassemia was carried out by automatic sequencing according to the Sanger’s method. Results. Genotypes have been classified into three groups according to the number of α-globin genes and the severity of the alteration in the β-globin gene. All had a mutation in the β-globin gene (β0-thalassemia, severe β+-thalassemia, and mild β+-thalassemia). Group I patients who have inherited 6 α globin genes. Group II and group III have inherited 5 α globin genes. In group III, the patients were carriers of mutations affecting the β and δ globin genes. The most significant hematological parameters were hemoglobin levels, mean corpuscular volume, red deep width, and percentage of fetal hemoglobin. Conclusions. In group I, patients who have inherited of 6 α globin genes, either by homozygous triplication (ααα/ααα) or heterozygous quadruplication (αααα/αα), with heterozygous β-thalassemia results in severe to moderate anemia that may require transfusion therapy, being the severity of the β-globin gene mutation that would determine the clinical variation. Group II patients behaved phenotypically like mild thalassemia intermedia. Finally, group III patients behaved like a thalassemic trait since all were carriers of mutations that increase the overexpression of g genes.

Estudio de la talasemia β en el laboratorio clínico: estrategias diagnósticas

“…Además, podemos encontrarnos con formas intermedias (β-tal intermedia) en pacientes con anemia no tan severa, como en las formas más graves, que no suelen requerir transfusiones (10).…”

“…β-tal intermedia: numerosas alteraciones moleculares pueden dar lugar a este fenotipo clínico. Aunque el diagnóstico sigue siendo en gran parte clínico, se ha descrito una asociación genotipo/fenotipo, de modo que la base genética de la diversidad fenotípica vendría determinada por moduladores genéticos (10).…”