Genetic and molecular diversity in nondeletion Hb H disease.

Restriction endonuclease mapping of nondeletion alpha-thalassemia determinants from a variety of racial groups showed no detectable abnormalities within a 40-kilobase region of the zeta-alpha globin gene cluster. By using a zeta-specific probe, we defined three different types of interactions that give rise to Hb H disease, each involving a nondeletion alpha-thalassemia haplotype. mRNA analysis showed further diversity within these groups, indicating that there are at least three nondeletion determinations.

Characterisation of a new alpha thalassemia 1 defect due to a partial deletion of the alpha globin gene complex.

A new deletion causing alpha thalassemia has been characterised in a Greek family. Detailed mapping of the alpha gene complex shows that the deletion extends for 5.2 kb and removes the whole of the alpha 2 gene and the 5' end of the alpha 1 gene. The affected chromosome, therefore produces no normal alpha chains and results in a phenotype of alpha thalassemia 1.

Occurrence of G gamma Hb F in Greek HPFH: analysis of heterozygotes and compound heterozygotes with beta thalassaemia.

Haemoglobin F has been isolated from the red cells of individuals with the Greek form of hereditary persistence of fetal haemoglobin (HPFH), and the glycine/alanine composition of the gamma CB3 peptides determined. In contrast to previous reports we have shown that the Hb F of the Greek HPFH heterozygotes contains significant amounts of G gamma chains and circumstantial evidence indicates that these are the products of the same chromosome that carries the Greek HPFH determinant. Hence this chromosome must be directing the synthesis of G gamma, A gamma and (probably) beta and delta chains, thus implying that the Greek form of HPFH does not result from a deletion involving the globin chain structural genes. Analysis of the levels and structure of Hb F from the Greek HPFH heterozygotes and from separated cell populations from the Greek HPFH/beta thalassaemia compound heterozygotes indicate that the Greek HPFH determinant, while allowing an overall increase in gamma chain synthesis, is not the sole factor determining the absolute amount of Hb F production on a cellular basis.

A comparison of the homozygous states for G gamma and G gamma A gamma delta beta thalassaemia.

One Arabic and two Indian patients with thalassaemia intermedia produce only Hb F for the G gamma type. Haemoglobin synthesis studies and genetic analysis indicate that they are homozygous for G gamma delta beta thalassaemia. The findings in these patients and their heterozygous relatives are compared with those in an individual homozygous for G gamma A gamma delta beta thalassaemia. From this analysis, and from previously reported data on G gamma A gamma delta beta thalassaemia, the phenotypic expression of the two varieties of delta beta thalassaemia is defined. The relationship between the clinical expression and molecular pathology of these forms of delta beta thalassaemia is discussed.