A Study of Some Genetic Ameliorating Factors in Beta Thalassemia

There are over 150 mutations affecting the beta globin gene that can lead to an altered expression of the gene and a decrease (β + ) or an absence (β 0) of beta globin production. The genes can be inherited in a homozygous or a heterozygous fashion. The result of inheritance of these genes can be diverse, ranging from beta thalassemia trait with no hematological disease to thalassemia major requiring repeated blood transfusions. There are co-inherited variables that can also influence the expression of this inheritance. Alpha gene deletion or the inheritance of the Gy Xmn-1 gene sequence (C-T variation) at position -158 upstream of the G (gamma)-globin gene which is detectable by the restriction enzyme XmnI, are among these variables. The aim of this study is to clarify the effect of the above two variables as ameliorating factors in homozygous/ double heterozygous beta thalassemia among a group of Egyptian thalassemic children. Thirty two cases of beta thalassemia were screened for common Mediterranean mutations (IVS1-110, 1-6,1-1, 11-745, codon 39, -87) ɑ-gene deletions, and presence of Gy Xmn-1 polymorphic site. As regards allele frequency, IVSI-6 showed the highest incidence (40.6%) followed by IVSI-110 (18.75%), IVSII-745 (12.5%), -87 (9.37%), IVSI-1 (3.12%) and codon 39 (0%). 7 cases (21.87%) were uncharacterized as regards to the 6 screened mutations. The co-inheritance of ɑ-thalassemia was found in 5 cases out of 32 cases (15.63%) and DNA polymorphism at -158 (C-T) of the gamma globin gene was demonstrated in 2/32 cases (6.25%). Both variables ameliorated the severity of the disease either in the form of decreased frequency of blood transfusion or delay in age of presentation or an amelioration of clinical severity of a known severe allele.