#604131
ICD+
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| ALPHA-THALASSEMIA | |||||||||||||||
| Phenotype Gene Relationships | |||||||||||||||
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| TEXT | |||||||||||||||
| A number sign (#) is used with this entry because of evidence that alpha-thalassemia is caused by mutations in the alpha-globin genes (HBA1, 141800; HBA2, 141850). Sequences 30 to 50 kb upstream from the alpha-globin gene cluster, referred to as the locus control region alpha (LCRA; 152422), have been found to be deleted in cases of alpha-thalassemia with structurally intact alpha-globin genes. The molecular and clinical aspects of the severe alpha-thalassemia syndromes were reviewed by Higgs (1993) and Chui and Waye (1998). Weatherall (2001) reviewed phenotype-genotype relationships in monogenic diseases based on studies of the thalassemias. The remarkable phenotypic diversity of the beta-thalassemias reflects the heterogeneity of mutations at the HBB locus, the action of many secondary and tertiary modifiers, and a wide range of environmental factors. Weatherall (2001) stated that phenotype-genotype relations will likely be equally complex in many monogenic diseases. The findings reviewed by Weatherall (2001) highlighted the problems that might be encountered in defining the relationship between the genome and the environment in multifactorial disorders, in which the degree of heritability may be relatively low and several environmental agents are involved. | |||||||||||||||
| Molecular Genetics | |||||||||||||||
| For a review of mutations in the HBA genes causing alpha-thalassemia, see 141800 and 141850. | |||||||||||||||
| REFERENCES | |||||||||||||||
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