Ma S K, Au W Y, Chan A Y, Chan L C
Division of Hematology, Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, P.R. China.
Int J Mol Med. 2001 Aug;8(2):171-5.
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.
α-珠蛋白基因额外拷贝的存在已被证明会加重β地中海贫血杂合子的贫血程度。我们描述了8名中国受试者的临床表型，他们同时携带三倍体α-珠蛋白基因和β0-地中海贫血等位基因的杂合性。他们是通过对中间型和重型β地中海贫血患者进行基因分型，以及通过香港基于社区的地中海贫血筛查项目确定的。采用标准分子技术确定基因型。本系列所有受试者均显示有5个α-珠蛋白基因拷贝（ααα/αα）与一个β0-地中海贫血等位基因相关联。尽管基因型相同，但6名受试者表现为中间型β地中海贫血表型，而2名在临床上与轻型β地中海贫血难以区分，这意味着存在尚未明确的遗传修饰因素。α-珠蛋白基因三倍体和β0-地中海贫血杂合性在我们当地的中间型β地中海贫血患者中占15%，且与轻度临床表型相关。在重型β地中海贫血患者中未发现这种基因型。他们在成年期发病，通常不依赖输血。与单纯的β地中海贫血杂合子相比，他们表现出明显的红细胞异常（低色素性、异形红细胞症、循环中幼红细胞）、较低的血红蛋白（Hb）水平和较高的HbF水平。对于症状比预期更明显的疑似β地中海贫血携带者，应始终考虑是否存在三倍体α-珠蛋白基因，以便避免对贫血原因进行不必要的检查。最后，对于仅一方在血红蛋白分析中表现为β地中海贫血的、有中间型β地中海贫血患儿的家庭，应检查是否存在α-珠蛋白基因三倍体。
