Ekwattanakit Supachai, Riolueang Suchada, Viprakasit Vip
a Division of Hematology, Department of Internal Medicine , Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand.
b Siriraj Integrated Center of Excellence for Thalassemia (SiiCOE-T) , Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok , Thailand.
Hematology. 2018 Mar;23(2):117-121. doi: 10.1080/10245332.2017.1359899. Epub 2017 Aug 3.
There are more than 200 known mutations found in patients with β-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia.
A comprehensive hematology and DNA analysis was applied in the index patient and her mother.
Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/β-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the β-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the β-globin gene which we named 'Hb Yala' according to the origin of this index family.
This mutation was assumed to generate a truncated β-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or β-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found.
This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.
在β地中海贫血患者中已发现200多种已知突变，识别未知或新突变的可能性越来越小。在此，我们报告一名来自泰国的患有慢性溶血性贫血患者的一种新突变。
对索引患者及其母亲进行了全面的血液学和DNA分析。
血液学和血红蛋白分析与Hb E/β地中海贫血的临床诊断一致。然而，使用我们常见的基于聚合酶链反应的β珠蛋白基因突变检测方法，我们仅发现了Hb E杂合突变。此外，分子分析显示β珠蛋白基因第二外显子第42密码子处有一个新的T缺失，根据该索引家族的起源，我们将其命名为“Hb Yala”。
该突变被认为产生了一个截短的β珠蛋白链，在第60密码子处终止，可能是不稳定变体，导致“无效”或β地中海贫血。然而，临床表型出人意料地轻微，未发现其他改善遗传因素，包括α地中海贫血的共遗传和Xmn I多态性导致的Hb F高倾向。
本报告提供了证据，表明地中海贫血综合征的基因型-表型相关性非常复杂，地中海贫血正确的临床严重程度分类应主要基于临床评估。
