title: Clinical phenotype of triplicated alpha-globin genes and heterozygosity for beta0-thalassemia in Chinese subjects.
abstract: The presence of extra copies of alpha-globin gene has been shown to worsen the degree of anemia in beta-thalassemia heterozygotes. We describe the clinical phenotype of eight Chinese subjects with heterozygosity for both triplicated alpha-globin gene and a beta0-thalassemia allele. They were identified through genotyping of beta-thalassemia intermedia and major patients, and through community-based thalassemia screening program in Hong Kong. Standard molecular techniques were used in the determination of genotype. All subjects in this series showed five copies of alpha-globin genes (alphaalphaalpha/alphaalpha) in association with a beta0-thalassemia allele. Although genotypically identical, six subjects showed a beta-thalassemia intermedia phenotype while two were clinically indistinguishable from beta-thalassemia minor, implying the presence of genetic modifying factors that remained undefined. Triplication of alpha-globin gene and heterozygosity for beta0-thalassemia accounted for 15% of beta-thalassemia intermedia patients at our locality and was associated with a mild clinical phenotype. This genotype was not found among beta-thalassemia major patients. They presented in adulthood and were usually not transfusion dependent. When compared with simple beta-thalassemia heterozygotes, they showed obvious red cell abnormalities (hypochromasia, anisopoikilocytosis, circulating normoblasts), lower hemoglobin (Hb) and higher HbF levels. The presence of triplicated alpha-globin genes should always be considered in apparent beta-thalassemia carriers who were more symptomatic than expected, so that unnecessary investigations for the cause of anemia could be avoided. Finally, triplication of alpha-globin genes should be looked for in families with children affected by beta-thalassemia intermedia in which only one parent showed a picture of beta-thalassemia on Hb analysis.
authors.affiliation: Division of Hematology, Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, P.R. China. eskma@hkucc.hku.hk
authors.forename: S K
authors.initials: SK
authors.lastname: Ma
authors.forename: W Y
authors.initials: WY
authors.lastname: Au
authors.forename: A Y
authors.initials: AY
authors.lastname: Chan
authors.forename: L C
authors.initials: LC
authors.lastname: Chan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D005260:Female; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D005914:Globins