Anna Metaxotou-Mavromati

The triplicated α‐globin gene locus in β‐thalassaemia heterozygotes: clinical, haematological, biosynthetic and molecular studies

Excess α‐globin chains play a major role in the pathophysiology of homozygous β‐thalassaemia. In β‐thalassaemia carriers a minor effect of α‐globin chain excess is reflected in a minimal or mild anaemia without clinical symptoms. Factors that increase α‐chain excess in heterozygotes are expected to accentuate the severity of the clinical and haematological phenotype.

The Corfu δβ thalassaemia mutation in Greece: haematological phenotype and prevalence

Summary The Corfu δβ thalassaemia mutation, a 7.2 kb deletion partially removing the (δ‐globin gene and a single nucleotide mutation (GA) at intervening sequence I (IVSI‐n5) in the β‐globin gene in cis, was first described in a family from Corfu; the carriers for this mutation had the unusual haematological phenotype of heterozygous β‐thalassaemia with normal levels of HbA2.

Prevalence of β0 and β+ Thalassemia Genes in Greek Children with Homozygous β-Thalassemia

In an attempt to estimate the prevalence of β0 and β+thalassemia genes in Greece chromatographic analysis of hemoglobins was performed in 30 children with homozygous β-thalassemia prior to any transfusion. In 13 (43%) no HbA was detected, suggesting the presence of β0 gene in the homozygous state (β0/β thal). In the remaining 17, HbA showed a bimodal distribution with values ranging from 4–36%. The detection of HbA suggests the presence of β+ gene, while the bimodal distribution could be explained by the assumption that the β+ gene in single dose and in combination with β0 gene (β0/β+ thai) results in the production of small amounts of HbA ranging from 4–11%, (first curve), while in double dose (β+/β+ thal), in the production of higher amounts of HbA ranging from 24–36% (second curve). The β0/β+ thai was observed in 11 (37%), and the β+/β+ thai in 6(20%). It is concluded that both β0 and β+genes are common in Greece and chromatographic analysis helps to determine the genotype of patients with homozygous β...

Globin gene mapping in normal Hb A2 types of beta-thalassaemia.

Globin‐gene mapping of DNA from 13 families with normal Hb A2β‐thalassaemia (both type 1 and type 2) failed to detect any difference from normal in their globin‐gene arrangement. We conclude that deletions such as those responsible for γβ‐thalassaemia or a ‘silent’ Hb Lepore are not responsible for this type of β‐thalassaemia in Greece.

The molecular basis of HbH disease in Greece

Summary. Globin gene mapping in 16 Greek individuals with HbH disease and their parents has demonstrated the occurrence of several HbH genotypes brought about by the interaction of two α+‐thalassaemia and two α+‐thalassaemia haplotypes. Eight of the 16 patients had the genotype Med/ ‐α3.7, four the genotype –(a)20.5/–α3.7 and three the genotype Med/aαT. In one patient the restriction data are consistent with two possible genotypes aαT/αTor /aαT. It is demonstrated that HbH disease in Greece is heterogeneous, with the deletion haplotypes Med and –α3.7 being more prevalent than the ‐(a)20.5 and non‐deletion (ααT) haplotypes.

Hematologic phenotype of the mutations IVS1-n6 (T-->C), IVS1-n110 (G-->A), and CD39 (C-->T) in carriers of beta-thalassemia in Greece.

The hematologic phenotype was characterized in heterozygotes for three of the most common beta-thalassemia mutations in the Greek population. The study included 17 carriers of beta++ IVS1-n6 (T-->C), 21 carriers of beta+ IVS1-n110 (G-->A), and 17 carriers of beta 0 CD39 (C-->T). The 55 beta-thalassemia heterozygotes were selected from among parents of patients on regular transfusion regimens, and the beta-thalassemia mutation was identified by means of the polymerase chain reaction to amplify the appropriate region of the beta-globin gene and then by allele-specific oligonucleotide hybridization. The assessment of hematologic phenotype included complete blood count and quantitation of hemoglobin HbA2 and HbF and of the globin chain biosynthesis ratio. Comparison and statistical analysis of the hematologic parameters for the three mutations demonstrated no consistent correlation among the three mutations relative to Hb levels, hematocrit, and red cell indices, although heterozygotes for the IVS1-n6 mutation produce red blood cells with slightly higher mean corpuscular volume; significantly lower values of HbA2 (mean, 3.81% +/- 0.62% with four values less than 3.60%) in IVS1-n6 heterozygotes compared with IVS1-n110 heterozygotes (mean, 4.69% +/- 0.48%) and CD39 heterozygotes (mean, 4.75% +/- 0.50%, P < 0.001); and significantly higher HbF levels in CD39 heterozygotes (mean, 2.31% +/- 1.52%) compared with IVS1-n6 heterozygotes (mean, 0.79% +/- 0.45%, P < 0.01) and IVS1-n110 heterozygotes (mean, 1.17% +/- 0.75%, P < 0.01). With respect to the HbA2 levels, the findings are in agreement with previous studies in Mediterranean populations; the slightly higher levels of HbF in CD39 heterozygotes appear to be reported for the first time.