Περίληψη:
The large degree of phenotypic heterogeneity of thalassemia can now be
related to the underlying genomic defects. This information has
accumulated rapidly over the last years through the recent advances in
molecular technology. The list of main types of thalassemia (alpha or
beta) that can be differentiated includes several gene deletions
(complete or partial) and point mutations (or very short deletions).
These occur within the genes or across the flanking DNA sequences and
apparently interfere with the expression of these genes. From a
quantitative point of view, the severity of the condition is directly
related to the amount of functional globin chain mRNA which is made
available to the ribosomes; this may vary from zero (gene deletions,
frameshift, non-sense mutations or mutations at the splice-junction
nucleotides) to very little (mostly hnRNA processing mutants) or to
slightly subnormal (transcriptional mutants, mutations resulting in
cryptic site activation or in defective cleavage of the poly-A tail). A
few hyper-unstable globin chains also produce a thalassemic phenotype.
This pattern is straightforward in the alpha-thalassemias. In the
beta-thalassemias, the decreased beta-chain synthesis reflects the
available mRNA, but the phenotypic expression depends also on the
ability of the patient to reactivate gamma-chain synthesis and
complement the red cell content with hemoglobin F.
