Relationship between genotype and phenotype. Thalassemia intermedia.
Thalassemia intermedia encompasses a number of clinical conditions ranging in severity from beta-thalassemia carrier state to transfusion-dependent thalassemia major. The molecular bases of thalassemia intermedia, only partially defined, are very heterogeneous, but in general any factor able to reduce the globin-chain imbalance results in a milder form of thalassemia. These factors are the presence of a silent or mild beta-thalassemia allele, associated with a high residual beta-globin production, and the coinheritance of alpha-thalassemia or of genetic determinants that increase the gamma-chain production. Less frequent mechanisms are double heterozygosity for beta-thalassemia and triplicated alpha genes, and the presence of a hyperunstable hemoglobin variant. However, for a consistent number of beta zero-thalassemia homozygotes with a thalassemia intermedia phenotype the modifying factor has not been defined yet. In contrast, there are simple beta-thalassemia carriers who, for unknown reasons, have an unusually severe clinical phenotype.
Istituto di Clinica e Biologia dell'Età Evolutiva, Ospedale Regionale, Cagliari, Italy. renzo.galanell@mcweb.unica.it
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D001803:Blood Transfusion; D005260:Female; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D017085:alpha-Thalassemia / Q000150:complications / Q000235:genetics / Q000628:therapy; D017086:beta-Thalassemia / Q000150:complications / Q000235:genetics* / Q000628:therapy
D005914:Globins