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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

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Abstract

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.

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Acknowledgements

We acknowledge the families for the collaboration. This study was supported by Ministero Istruzione, Università e Ricerca (MIUR), Legge 488/92, Cluster C02, Project 2.

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Authors and Affiliations

  1. Istituto di Genetica e Biofisica “Adriano Buzzati Traverso”, CNR, Via Pietro Castellino 111, 80131, Naples, Italy

    Giuseppina Lacerra, Gennaro Musollino, Romeo Prezioso & Clementina Carestia

  2. I° Laboratorio Analisi Chimico-Cliniche, Ospedali Riuniti, Azienda Ospedaliera-Universitaria, Foggia, Italy

    Clelia Scarano

  3. Servizio di Talassemia ed Emoglobinopatie, Azienda Ospedaliero-Universitaria Policlinico “Gaspare Rodolico”, Catania, Italy

    Rosario Testa & Daniela G. Caruso

  4. Servizio di Thalassemia, P.O. Garibaldi, ARNAS “Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli”, Catania, Italy

    Laura F. Lagona & Emilia Medulla

  5. Centro Trasfusionale e di Microcitemia, Azienda Ospedaliera Ospedali Civili Riuniti, Sciacca (Agrigento), Italy

    Maria G. Friscia

  6. U.O.S. di Microcitemia, Ospedale “Madonne delle Grazie”, Matera, Italy

    Carlo Gaudiano

Authors
  1. Giuseppina Lacerra
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  2. Clelia Scarano
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  3. Gennaro Musollino
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  4. Rosario Testa
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  5. Romeo Prezioso
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  6. Daniela G. Caruso
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  7. Laura F. Lagona
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  8. Emilia Medulla
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  9. Maria G. Friscia
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  10. Carlo Gaudiano
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  11. Clementina Carestia
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Correspondence to Giuseppina Lacerra.

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Lacerra, G., Scarano, C., Musollino, G. et al. 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. Ann Hematol 89, 127–134 (2010). https://doi.org/10.1007/s00277-009-0784-9

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  • DOI: https://doi.org/10.1007/s00277-009-0784-9

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