Co-inheritance of α and β-Thalassemia in a Jordanian Family

Extract

Additional α-genes may increase the severity of heterozygous β-thalassemia. Conversely, the co-inheritance of α-thalassemia with homozygous β-thalassemia and the consequent reduction in α-globin chain excess often results in a milder clinical and haematological phenotype. This study describes the hematological and the molecular data resulting from the interaction between α and β⁺ -thalassemia determinants in a Jordanian family. The parents are double heterozygotes for α and β-thalassemia. DNA analysis of four children characterized homozygosity for β⁺ IVS 1.6 thalassemia mutation in three of them. Co-existing heterozygosity for -α ^3.7 was detected in two of them (Children 1 and 2). Those two children have a less severe clinical course than that of the third child (Child 3) with homozygosity for β-thalassemia only. The co-existence of -α ^3.7 mutations with homozygous β-thalassemia may have converted a transfusion-dependent thalassemia major to non transfusion-dependent thalassemia intermedia. The fourth child (Child 4) was heterozygous for -α ^3.7 but lacked β⁺ IVS 1.6 mutation and appeared normal.

Human globin-gene mutations are amongst the most common genetic disorders observed in human populations.¹ At the molecular level β-thalassemia comprises a heterogeneous group of hemoglobin disorders resulting from mutations eliminating (β^o) or reducing (β⁺) the β-globin gene expression. Over 200 different mutations can cause β-thalassemia phenotype.²

Of the numerous mutations that have been described to cause α-thalassemia phenotype, deletions at the α-gene locus account for the vast majority of α-thalassemia alleles.³ The most widely occurring single-gene deletions are the -α^3.7 and the -α^4.2, while the double α-gene deletions in cis,…

ABBREVIATIONS: MCH = mean corpuscular hemoglobin; MCV = mean corpuscular volume; PCR = polymerase chain reaction.