title: Molecular mechanisms of thalassemia in southeast Asia.
abstract: Hemoglobinopathies are the most common genetic disorders in Southeast Asia. alpha-Thalassemia is most often due to a alpha-globin gene deletion. Hb Constant Spring (CS) occurs from the mutation at the termination codon of the alpha-globin gene resulting in an elongated polypeptide; alpha(CS)-globin mRNA is also unstable and only small amounts of Hb CS are produced. Thus Hb CS has an alpha-thalassemia 2-like effect. beta-Thalassemia results from a variety of molecular mechanisms, most of which are single base substitutions or deletions or insertions of one to four nucleotides. Hemoglobin E occurs from a Glu --> Lys substitution at position 26 of the beta-globin chain. The abnormal gene also results in reduced amounts of beta E-mRNA and hence of beta E-globin chains. Therefore, Hb E has a mild beta + thalassemia phenotype. Homozygous beta-thalassemia and beta-thalassemia/Hb E are the major beta-thalassemic syndromes in Southeast Asia. In spite of seemingly identical genotypes, severity of beta-thalassemia/Hb E patients can vary greatly. Some may have a severe clinical disorder approaching that seen in homozygous beta-thalassemia. A number of genetic factors have been shown to determine the differences in severity of anemia in beta-thalassemia/Hb E, including co-inheritance of alpha-thalassemia determinants and co-inheritance of other determinants which elevate Hb F expression. A correlation between the extent of beta E-globin mRNA cryptic splicing and the severity of anemia in beta(zero)-thalassemia/Hb E patients has been observed. Complete characterization of mutations causing hemoglobinopathies will help to bolster the establishment of prenatal diagnosis of these genetic disorders in the region.
authors.affiliation: Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Winichagoon
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: P
authors.initials: P
authors.lastname: Wilairat
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D017398:Alternative Splicing; D001210:Asia, Southeastern; D005006:Ethnicity; D005319:Fetal Hemoglobin / Q000235:genetics; D017353:Gene Deletion; D005843:Geography; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017354:Point Mutation; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin