Role of nonsense-mediated decay and nonsense-associated altered splicing in the mRNA pattern of two new α-thalassemia mutants.

α-thalassemia is a common disease characterized mainly by deletion mutants. We identified two new α-thalassemia pointform mutants: α1cod22 GGC>GGT Gly>Gly creating a 5' splicing sequence and α1cod23 GAG>TAG Glu>stop. We performed qualitative and semi-quantitative analysis of the mRNA molecules, from carriers' blood, to define the molecular mechanisms giving rise to the thalassemia phenotype.

Identification and molecular characterization of a novel 163 kb deletion: The Italian (ϵγδβ)(0)-thalassemia.

Objective And Importance: To verify the presence of β-thalassemia in subjects showing hematologic phenotype of α-thalassemia, conduct normal molecular sequence analysis of the α-globin genes, and detect the absence of the most frequent α-thalassemia deletions.

Clinical Presentation: A patient from Apulia (Southern Italy) was referred to our institution for the occasional founding of hypochromic polyglobulia and microcytic red blood cells associated with normal levels of Hb A2 and Hb F and normal iron parameters.

Intervention And Technique: The patient has been investigated using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), quantitative real-time PCR, restriction analysis, and gap-PCR.

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.

Hb Foggia or alpha 117(GH5)Phe -> Ser: a new alpha 2 globin allele affecting the alpha Hb-AHSP interaction.

We report a novel alpha2-globin gene allele with the mutation cod 117 TTC>TCC or alpha 117(GH5)Phe>Ser detected in three carriers with alpha-thalassemia phenotype. The mutated mRNA was present in the reticulocytes in the same amount as the normal one, but no chain or hemoglobin variant were detected. Most likely the amino acid substitution impairs the interaction of the alpha-chain variant with the AHSP and prevents its stabilizing effect, thus leading to the alpha-chain pool reduction.