T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation
T-cell lines from 2 patients with adenosine deaminase (ADA) deficiency showed the restoration of ADA activity resulted from the reversion of an inherited mutation
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DOI：
10.1182/blood.v97.9.2896
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发表时间：
2001-05-01
期刊：
影响因子：
20.3
通讯作者：
Sakiyama, Y
中科院分区：
文献类型：
--
作者：
Ariga, T;Oda, N;Sakiyama, Y
遗传性腺苷脱氨酶（ADA）缺陷导致一种常染色体隐性形式的严重联合免疫缺陷。本文讨论了2例ADA缺乏症患者，他们来自不同的家庭，其中可能发生了回复突变。在患者的ADA基因中发现了新的突变，他们的父母都是携带者。出乎意料的是，建立的患者T细胞系，而不是B细胞系，显示出一半正常水平的ADA酶活性。对这些T细胞系中突变的重新评估表明，两名患者中的一种遗传性ADA基因突变发生了逆转。至少有一名患者似乎在体内拥有回复突变体细胞;然而，突变细胞可能在接受ADA酶替代治疗后克服了回复突变体。这些发现可能对ADA缺乏症的干细胞基因治疗前景具有重要意义。（Blood，2001; 97：2896 - 2899）（C）2001年美国血液学会。
Inherited deficiency of adenosine deaminase (ADA) results in one of the autosomal recessive forms of severe combined immunodeficiency. This report discusses 2 patients with ADA deficiency from different families, in whom a possible reverse mutation had occurred. The novel mutations were identified in the ADA gene from the patients, and both their parents were revealed to be carriers. Unexpectedly, established patient T-cell lines, not B-cell lines, showed half-normal levels of ADA enzyme activity. Reevaluation of the mutations in these T-cell lines indicated that one of the inherited ADA gene mutations was reverted in both patients. At least one of the patients seemed to possess the revertant cells in vivo; however, the mutant cells might have overcome the revertant after receiving ADA enzyme replacement therapy. These findings may have significant implications regarding the prospects for stem cell gene therapy for ADA deficiency. (Blood, 2001;97:2896-2899) (C) 2001 by The American Society of Hematology.