1. HbA2-Partinico or δ(A2)Pro→Thr, a new genetic variation in the δ-globin gene 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
- Author
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Laura F. Lagona, Carlo Gaudiano, Clementina Carestia, Giuseppina Lacerra, Daniela Caruso, Maria G. Friscia, Clelia Scarano, Romeo Prezioso, Emilia Medulla, Gennaro Musollino, R. Testa, Istituto di Genetica e Biofisica 'Adriano Buzzati Traverso' (IGB), Consiglio Nazionale delle Ricerche (CNR), I° Laboratorio Analisi Chimico-Cliniche, Ospedali Riuniti, Azienda Ospedaliera-Universitaria, Servizio di Talassemia ed Emoglobinopatie, Azienda Ospedaliero-Universitaria Policlinico 'Gaspare Rodolico', Servizio di Thalassemia, P.O. Garibaldi, ARNAS 'Garibaldi, S. Luigi-Currò, Ascoli-Tomaselli', Centro Trasfusionale e di Microcitemia, Azienda Ospedaliera Ospedali Civili Riuniti, U.O.S. di Microcitemia, and Ospedale 'Madonne delle Grazie'
- Subjects
Genetics ,Hb-HPLC ,AATAA%22">δ thal AATAA>AATAA ,Haplotype ,Hematology ,General Medicine ,Biology ,HbA2 variants ,Molecular biology ,β-thalassemia carriers screening ,03 medical and health sciences ,0302 clinical medicine ,TAG%22">δ° thal cod 15 TGC>TAG ,Polymorphism (computer science) ,030220 oncology & carcinogenesis ,Genetic variation ,HbA2-Partinico ,Gene conversion ,Globin ,Restriction fragment length polymorphism ,Allele ,Gene ,030215 immunology - Abstract
The study of the alleles of the delta-globin gene is relevant to the prevention of beta-thalassemia homozygosis; in fact, the increase of the HbA2 is an invaluable hematological marker of the beta-thalassemia heterozygosis and the double heterozygosis for alleles of delta- and beta-globin genes can cause the decrease of the HbA2 up to normal or borderline values. We carried out the characterization of alleles of the delta- and beta-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 delta-globin alleles was detected; seven known alleles in trans to the beta-globin gene defects were revealed in 17 out of 18 families, while a new allele in cis to a beta-thalassemia allele was detected in one family. Moreover, the relative frequency of the delta-mutants was quite different from that found among heterozygotes. The new allele delta-cod 5 CCT>ACT, in cis to the allele beta(+) thal IVS-I-110 G>A, was found in five carriers of a Sicilian family. The new variant delta5(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 beta(+) thal IVS-I-110 G>A, even if crossing over or gene conversion cannot be excluded.
- Published
- 2009
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