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

• Published in: Annals of hematology Vol. 89; no. 2; pp. 127 - 134
• Main Authors: Lacerra, Giuseppina, Scarano, Clelia, Musollino, Gennaro, Testa, Rosario, Prezioso, Romeo, Caruso, Daniela G, Lagona, Laura F, Medulla, Emilia, Friscia, Maria G, Gaudiano, Carlo, Carestia, Clementina
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.02.2010; Springer-Verlag
• Subjects: Adolescent; Adult; Aged; Alleles; beta-Globins - genetics; beta-Thalassemia - genetics; Child; delta-Globins - genetics; Female; Haplotypes - genetics; Hematology; Heterozygote; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation - genetics; Oncology; Original Article; Pedigree; Polymorphism, Restriction Fragment Length; Young Adult; AA; δ° thal cod 15 TGC>TAG; HbA2 variants; δ; thal AAT; Hb-HPLC; AA>AAT; HbA2-Partinico; β-thalassemia carriers screening
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-009-0784-9

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.