Schilirò G, Di Gregorio F, Samperi P, Mirabile E, Liang R, Cürük M A, Ye Z, Huisman T H
Division of Pediatric Hematology and Oncology, University of Catania, Sicily, Italy.
Am J Hematol. 1995 Jan;48(1):5-11. doi: 10.1002/ajh.2830480103.
In this study we have defined the spectrum of the beta-thalassemia mutations, the beta-thalassemia haplotypes, and the genotype-to-phenotype correlations in a large number of patients with different beta-thalassemia conditions. Seventeen different beta-thalassemia mutations were detected which included one chromosome each with Hb Dhonburi and Hb Lepore. Five alleles, namely, codon 39 (C-->T), IVS-I-110 (G-->A), IVS-I-6 (T-->C), IVS-II-745 (C-->G), and IVS-I-1 (G-->A), account for 90% of all beta-thalassemia mutations in 846 thalassemic chromosomes studied. Haplotyping for a large number of subjects showed that the five common mutations are linked to a few haplotypes. The presence of milder mutations, mainly IVS-I-6 (T C), in about 19% of our patients explains some of the clinical variables. Among the 37 patients with thalassemia of intermediate severity, only 6 were homozygous or compound heterozygous for two severe alleles. The type of beta-thalassemia is the main factor responsible for differences in the phenotypic expression of the disease in patients with Hb S-beta-thalassemia; patients with Hb S-beta(+)-thalassemia are less severely affected than those with Hb S-beta(0)-thalassemia. The five most frequent mutations have comparable distributions all over Sicily.
在本研究中，我们确定了大量不同β地中海贫血病症患者的β地中海贫血突变谱、β地中海贫血单倍型以及基因型与表型的相关性。检测到17种不同的β地中海贫血突变，其中包括各一条携带Hb Dhonburi和Hb Lepore的染色体。在研究的846条地中海贫血染色体中，5个等位基因，即密码子39（C→T）、IVS-I-110（G→A）、IVS-I-6（T→C）、IVS-II-745（C→G）和IVS-I-1（G→A），占所有β地中海贫血突变的90%。对大量受试者进行单倍型分析表明，这5种常见突变与少数单倍型相关。约19%的患者存在较轻的突变，主要是IVS-I-6（T→C），这解释了一些临床变量。在37例中度严重程度的地中海贫血患者中，只有6例为两个严重等位基因的纯合子或复合杂合子。β地中海贫血的类型是导致Hb S-β地中海贫血患者疾病表型表达差异的主要因素；Hb S-β（+）-地中海贫血患者的病情比Hb S-β（0）-地中海贫血患者轻。这5种最常见的突变在西西里岛各地的分布相当。
