HbA2-Partinico or δ(A2)Pro→Thr, a new genetic variation in the δ-globin gene in cis to the β+ thal IVS-I-110 G>A, and the heterogeneity of δ-globin alleles in double heterozygotes for β- and δ-globin gene defects

The study of the alleles of the δ-globin gene is relevant to the prevention of β-thalassemia homozygosis; in fact, the increase of the HbA2 is an invaluable hematological marker of the β-thalassemia heterozygosis and the double heterozygosis for alleles of δ- and β-globin genes can cause the decrease of the HbA2 up to normal or borderline values. We carried out the characterization of alleles of the δ- and β-globin genes, restriction fragment length polymorphism (RFLP) haplotype background, and hematologic phenotype in 23 double heterozygotes belonging to 18 unrelated families. A wide heterogeneity of the δ-globin alleles was detected; seven known alleles in trans to the β-globin gene defects were revealed in 17 out of 18 families, while a new allele in cis to a β-thalassemia allele was detected in one family. Moreover, the relative frequency of the δ-mutants was quite different from that found among heterozygotes. The new allele δ-cod 5 CCT>ACT, in cis to the allele β+ thal IVS-I-110 G>A, was found in five carriers of a Sicilian family. The new variant δ5(A2)Pro→Thr, named HbA2-Partinico upon the origin of the family, was detected with high-performance liquid chromatography; it overlapped the HbA2 peak which was partially split. The double in cis heterozygotes had increased percentage of normal and variant HbA2 of comparable size. The variant originated most likely from a new mutational event because it was associated with RFLP haplotype I, commonly found with the β+ thal IVS-I-110 G>A, even if crossing over or gene conversion cannot be excluded. [ABSTRACT FROM AUTHOR]