Kanavakis E, Traeger-Synodinos J, Tzetis M, Metaxotou-Mavromati A, Ladis V, Kattamis C
First Department of Pediatrics, Athens University, St Sophia's Children's Hospital, Greece.
Pediatr Hematol Oncol. 1995 Jan-Feb;12(1):37-45. doi: 10.3109/08880019509029526.
Homozygous beta-thalassemia is usually characterized by severe anemia requiring regular blood transfusion for survival. For homozygous patients with milder clinical manifestations and no dependence on transfusion therapy, the term thalassemia intermedia is usually applied. Genetic mechanisms that may ameliorate the clinical expression of homozygous beta-thalassemia include coinheritance of alpha-thalassemia, inheritance of mild beta-globin gene mutations, and increased gamma-globin chain production, which may partially compensate for the lack of beta-globin chain synthesis. To identify which of these factors may contribute to the modification of childhood homozygous, high-hemoglobin A2 (HbA2) beta-thalassemia in Greece, the interaction of alpha-thalassemia, types of beta-thalassemia mutations, and the presence of a polymorphic site 5' to the G gamma-globin gene, which has been described as associated with increased gamma-globin chain production in some cases, was assessed. The results were analyzed in light of similar studies in 150 randomly selected, homozygous, high-HbA2 beta-thalassemia patients with the aim of assessing whether thalassemia genotypes can provide information useful for prognosis and/or more appropriate management of homozygous beta-thalassemia patients. The results indicate that, in general, the major factor modifying the clinical expression of homozygous, high-HbA2 beta-thalassemia in Greece is the inheritance of mild beta-thalassemia mutations. Although there is not always a complete correlation of genotype with clinical phenotype, the inheritance of two mild beta-thalassemia alleles results in almost all cases (11 of 12 cases in this study) in thalassemia intermedia phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
纯合子β地中海贫血通常的特征是严重贫血，需要定期输血以维持生命。对于临床表现较轻且不依赖输血治疗的纯合子患者，通常使用“中间型地中海贫血”这一术语。可能改善纯合子β地中海贫血临床表型的遗传机制包括α地中海贫血的共遗传、轻度β珠蛋白基因突变的遗传以及γ珠蛋白链产量增加，后者可部分补偿β珠蛋白链合成的缺乏。为了确定这些因素中哪些可能有助于改变希腊儿童纯合子、高血红蛋白A2（HbA2）β地中海贫血的表型，评估了α地中海贫血、β地中海贫血突变类型以及Gγ珠蛋白基因5'端一个多态性位点（在某些情况下该位点与γ珠蛋白链产量增加有关）之间的相互作用。对150例随机选择的纯合子、高HbA2β地中海贫血患者进行了类似研究，并分析结果，目的是评估地中海贫血基因型是否可为纯合子β地中海贫血患者的预后和/或更恰当的治疗提供有用信息。结果表明，总体而言，改变希腊纯合子、高HbA2β地中海贫血临床表型的主要因素是轻度β地中海贫血突变的遗传。虽然基因型与临床表型并不总是完全相关，但两个轻度β地中海贫血等位基因的遗传在几乎所有病例中（本研究12例中的11例）都导致中间型地中海贫血表型。（摘要截选至250字）
