Fisher Christopher A, Premawardhena Anuja, de Silva Shanthimala, Perera Giathra, Rajapaksa Shabna, Olivieri Nancy A, Old John M, Weatherall David J
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Br J Haematol. 2003 May;121(4):662-71. doi: 10.1046/j.1365-2141.2003.04346.x.
The beta-globin gene mutations and the alpha-globin genes of 620 patients with the phenotype of severe to moderate thalassaemia from seven centres in Sri Lanka were analysed. Twenty-four beta-globin gene mutations were identified, three accounting for 84.5% of the 1240 alleles studied: IVSI-5 (G-->C) 56.2%; IVSI-1 (G-->A) 15.2%; and haemoglobin E (codon (CD)26 GAG-->GAA) 13.1%. Three new mutations were found; a 13-bp deletion removing the last nucleotide in CD6 to CD10 inclusively, IVSI-129 (A-->C) in the consensus splice site, and a frame shift, CD55 (-A). The allele frequency of alpha+ thalassaemia was 6.5% and 1.1% for -alpha3.7 and -alpha4.2 deletions respectively. Non-deletion alpha-thalassaemia was not observed. Triplicate or quadruplicate alpha-globin genes were unusually common. In 1.5% of cases it was impossible to identify beta-thalassaemia alleles, but in Kurunegala detailed family studies led to an explanation for the severe thalassaemia phenotype in every case, including a previously unreported instance of homozygosity for a quadruplicated alpha-globin gene together with beta-thalassaemia trait. These findings have implications for the control of thalassaemia in high-frequency populations with complex ethnic histories.
对来自斯里兰卡七个中心的620例重度至中度地中海贫血表型患者的β-珠蛋白基因突变和α-珠蛋白基因进行了分析。共鉴定出24种β-珠蛋白基因突变，其中三种在研究的1240个等位基因中占84.5%：IVSI-5（G→C）占56.2%；IVSI-1（G→A）占15.2%；血红蛋白E（密码子（CD）26 GAG→GAA）占13.1%。发现了三种新突变；一种13bp的缺失，包含CD6至CD10的最后一个核苷酸；共有剪接位点的IVSI-129（A→C）；以及一个移码突变CD55（-A）。α+地中海贫血的等位基因频率，-α3.7缺失为6.5%，-α4.2缺失为1.1%。未观察到非缺失型α地中海贫血。α珠蛋白基因的三重或四重重复异常常见。在1.5%的病例中无法鉴定出β地中海贫血等位基因，但在库鲁内格勒进行的详细家系研究对每个病例的重度地中海贫血表型都做出了解释，包括一个先前未报道的四倍体α珠蛋白基因纯合子与β地中海贫血特征的病例。这些发现对控制具有复杂种族历史的高频人群中的地中海贫血具有重要意义。
