Winichagoon P, Fucharoen S, Wilairat P, Chihara K, Fukumaki Y
Department of Medicine, Faculty of Medicine Siriraj Hospital, Institute of Sciences and Technology for Research and Development, Mahidol University, Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 1995;26 Suppl 1:241-5.
In spite of seemingly identical genotypes, severity of beta-thalassemia/hemoglobin (Hb) E patients can vary greatly. Some may have a severe clinical disorder approaching that seen in homozygous beta-thalassemia. Since mutation in codon 26 of the beta E-globin gene can lead to an alternative splicing, Hb E acts like a mild beta(+)-thalassemia. Variation in the amount of beta E-globin mRNA may also govern the difference in severity of anemia in beta-thalassemia/Hb E patients who otherwise have the same genetic determinants. We have determined the percentage of the alternatively spliced beta E-globin mRNA by the RT-PCR technique in 14 patients and found that the amount of abnormal spliced beta E-globin mRNA in those patients with severe symptoms ranged between 2.9 to 6.1%, whereas those with milder symptoms had the values which ranged between 1.6 to 2.6%. The extent of beta E-globin mRNA cryptic splicing was better associated with clinical severity of the patients than did the patterns of the Xmn I polymorphism at position -158 of the G gamma-globin gene or levels of Hb F.
尽管β地中海贫血/血红蛋白E（Hb E）患者的基因型看似相同，但其病情严重程度却可能有很大差异。有些患者可能患有严重的临床疾病，接近纯合子β地中海贫血患者的病情。由于βE珠蛋白基因第26密码子的突变可导致异常剪接，Hb E的作用类似于轻度β（+）地中海贫血。βE珠蛋白mRNA数量的差异也可能决定了具有相同遗传决定因素的β地中海贫血/Hb E患者贫血严重程度的差异。我们运用逆转录聚合酶链反应（RT-PCR）技术测定了14例患者中异常剪接的βE珠蛋白mRNA的百分比，发现症状严重的患者中异常剪接的βE珠蛋白mRNA的量在2.9%至6.1%之间，而症状较轻的患者其值在1.6%至2.6%之间。与Gγ珠蛋白基因-158位Xmn I多态性模式或Hb F水平相比，βE珠蛋白mRNA隐蔽剪接的程度与患者的临床严重程度相关性更好。
