Familial essential thrombocythemia associated with one-base deletion in the 5′-untranslated region of the thrombopoietin gene
Familial essential thrombocythemia associated with one-base deletion in the 5′-untranslated region of the thrombopoietin gene
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DOI：
10.1182/blood.v92.4.1091.416a36_1091_1096
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发表时间：
1998-08-15
期刊：
影响因子：
20.3
通讯作者：
Asaka, M
中科院分区：
文献类型：
--
作者：
Kondo, T;Okabe, M;Asaka, M
家族性原发性血小板增多症(ET)以常染色体显性遗传。这一发现表明，家族性ET可能是由于激活血小板生成的突变(S)所致。1994年，血小板生成素(TPO)基因被分离克隆。TPO-TPO受体由c-MPL基因编码，是血小板生成的重要调节因子，因此TPO或c-MPL的改变可能是导致常见ET的致病事件。此外，我们在TPO基因的5‘-非翻译区中发现了一个碱基缺失，在受影响的家庭成员中没有。体外实验表明，已鉴定的突变增加了TPO的产生。根据我们的发现，我们认为TPO基因的这个区域可能在调节TPO的表达中起着关键作用，我们的结果强烈地表明该突变导致了家族性ET。(C)1998年由美国血液病学会主办。
Familial essential thrombocythemia (ET) is inherited in an autosomal-dominant manner. This finding implies that familial ET may arise as a consequence of a mutation(s) that activates platelet production. In 1994, the thrombopoietin (TPO) gene was isolated and cloned. The TPO-TPO receptor, encoded for by the c-mpl gene, are essential regulators of thrombopoiesis, Alterations of TPO or c-Mpl thus may constitute a pathogenic event leading to familiar ET in a case of familial ET presented in our institute, serum TPO levels were significantly elevated in affected members of the family as compared with nonaffected members. Moreover, we identified a one-base deletion in the 5'-untranslated region of the TPO gene in affected but not in nonaffected family members. In vitro experiments showed that the identified mutation increased TPO production. Based on our findings, we propose that this region of the TPO gene may play a crucial role in regulating TPO expression, Our results strongly suggest that the identified mutation leads to familial ET. (C) 1998 by The American Society of Hematology.