The preferential removal of the mutant alpha-globin explains the reduced level of haemoglobin Hasharon found in subjects carrying the gene for beta-thalassaemia (Alberti et al, 1975).
The alpha globin genotypes of 55 beta thalassaemia heterozygotes have been determined by restriction endonuclease analysis to identify those with interacting alpha thalassaemia genes.
These findings support the theory that coinheritance of alpha-thalassemia mitigates the severity of beta-thalassemia and suggest that the protection is most pronounced when two alpha-globin genes are deleted.
This could be a direct result of the gene defect producing beta-thalassemia or be due to differences in the delta-globin gene linked to this beta-thalassemia gene.
The synthesis of delta-globin is directed by a gene whose inherent characteristics permit only limited expression, a gene resembling in some respects that of beta +-thalassemia.
On the other hand, the combination of the homozygous state for the triple alpha-globin gene loci and the heterozygous state for beta-thalassemia produced a clinical picture of thalassemia intermedia with a very mild clinical course, minor increase of fetal hemoglobin (HbF) levels, and a pronounced imbalance of globin chain synthesis.
This paper reports a Sardinian patient, who was a compound heterozygote for silent beta-thalassaemia and high Hb A2 beta o-thalassaemia with the clinical phenotype of mild thalassaemia intermedia; alpha globin gene mapping showed a single alpha globin gene deletion.
These indicated that the fetus was heterozygous for beta thalassaemia and had deletion of three alpha globin structural genes, while the mother, heterozygous for beta thalassaemia, also had deletion of two alpha globin structural genes.
In this paper we report that the combination of a triplicated alpha globin locus with heterozygous beta-thalassaemia produces a clinical phenotype of thalassaemia intermedia in five Italian subjects from four unrelated families, while in two other cases the phenotype was thalassaemia minor.
Ferrokinetic studies, alpha globin gene mapping, and assessment of iron status have been carried out in 16 healthy subjects with heterozygous beta thalassaemia.
As the type of Hb Lepore was the same in all patients (Lepore-Boston-Washington) and an alpha-globin gene deficiency was absent, it was concluded that the type of beta-thalassaemia determined the severity of the disease.
Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians.
Other variant hemoglobins including beta thalassemia are rare, but alpha thalassemia occurs in 39% (32% with 3 alpha-globin genes; 7% with 2 alpha-globin genes).
Characterization of the beta-thalassemia mutation in combination with alpha-globin mapping and haplotype analysis may allow a better estimate of the probability of a given clinical phenotype, thus permitting more accurate counseling.
In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 beta thalassaemia and the beta th-101 mutation in combination with the triple alpha globin gene arrangement.
Identification of deletion and triple alpha-globin gene haplotypes in the Montreal beta-thalassemia screening program: implications for genetic medicine.
From these results, we may conclude that the inheritance of a mild beta-thalassemia allele such as the beta+ IVS-I nt 6 mutation, in the homozygous or heterozygous state, the coinheritance with homozygous beta zero-thalassemia of the -158 (C----T) G gamma gene promoter mutation and the presence of heterozygous beta-thalassemia/triple alpha-globin gene arrangement are the most common reasons accounting for the development of attenuated forms of beta-thalassemia in Puglia.
Several members had additional beta-chain abnormalities (Hb S, Hb D-Los Angeles, beta-thalassaemia); the 11 persons with a Hb S heterozygosity and various alpha-globin gene defects (-alpha/alpha alpha; alpha T alpha/alpha alpha, - -/alpha alpha, -alpha/-alpha and - -/alpha T alpha) showed a decrease in the level of Hb S that was directly related to the severity of the alpha-chain deficiency.
During a screening program to identify at risk couples for beta-thalassemia first-trimester prenatal diagnosis, we were able to detect, by polymerase chain reaction (PCR) and direct genomic sequencing of the PCR product, a homozygosis for the G-T substitution at the first nucleotide of codon 27 of the delta-globin gene in a pregnant Sicilian woman.
We report the clinical, haematological, biosynthetic and molecular data in three beta-thalassaemia heterozygotes with the rare interaction of homozygosity for alpha-globin gene triplication, and in 17 heterozygotes with a single additional alpha-globin gene.
The delta-mRNA levels correlated inversely with hemoglobin and red cell indices but directly with HbA(2) levels in heterozygotes of each of the group of beta-thalassemia mutations.
The main pathophysiologic feature of beta-thalassemia is the accumulation of unpaired alpha-globin chains in erythrocyte precursors and red blood cells (RBCs).
It has been estimated that 13% to 33% of Sardinians carry a mutant allele of the alpha-globin gene (alpha-thalassemia trait) and that 6% to 17% are beta-thalassemia carriers.