α-Thalassemia associated with hb instability: a tale of two features. the case of Hb Rogliano or α1 Cod 108(G15)Thr→Asn and Hb Policoro or α2 Cod 124(H7)Ser→Pro.

We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain.

Genotype-phenotype relationship of the δ-thalassemia and Hb A(2) variants: observation of 52 genotypes.

The increase of Hb A(2) (α2δ2) beyond the upper limit [2.0-2.2/3.

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

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.

Molecular evidences of single mutational events followed by recurrent crossing-overs in the common delta-globin alleles in the Mediterranean area.

The human delta-globin gene (HBD) is one of the beta-like globin genes expressed in adults. In the Mediterranean countries the carriers of delta-thalassemia defects or Hb A2-variants are >1% and about 40/70 known alleles have been found in families with this ethnic origin. The scope of this study was to investigate the variability of the gene and of the chromosomal background in order to highlight the origin and spreading of the delta-globin gene alleles in the Mediterranean area.