Molecular pathology and detection of beta-thalassemias.
In this review, we have described the molecular bases accounting for beta, delta beta and gamma delta beta-thalassemias, discussed the molecular mechanisms responsible for the production of mild forms of thalassemia and presented a strategy for detecting beta-thalassemia mutations in each at risk population. The molecular bases of beta-thalassemia are very heterogeneous. The great majority of beta-thalassemias are caused by point mutations affecting the coding region or critical areas of the beta-globin gene and are only rarely produced by gross gene rearrangements. By contrast delta beta and gamma delta beta-thalassemias most commonly result from gross gene deletion. Determinants recognized to date as able to produce mild forms of beta-thalassemias, are beta-thalassemia mutations with a high residual output of beta-globin chain production, coinheritance of alpha-thalassemia or nondeletion HPFH linked or not linked to the beta-globin gene cluster, delta beta thalassemias and specific beta-globin haplotype. Because in each population a restricted number of molecular defect occurs, strategies have been developed to detect the beta-thalassemia mutations in prospective parents in each at risk population. These strategies are based on the direct detection of the mutation by dot blot analysis on enzymatically amplified DNA using a limited number of oligonucleotide probes complementary to the most common mutations in each population.
Cao
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A
Istituto di Clinica e Biologia dell'Età Evolutiva, Università Studi Cagliari, Italy.
Murru
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S
D000483:Alleles; D002872:Chromosome Deletion; D005820:Genetic Testing; D005914:Globins / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D009154:Mutation; D013789:Thalassemia / Q000235:genetics*
D005914:Globins