Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria
Molecular basis of the heterogeneity of expression of glycosyl phosphatidylinositol anchored proteins in paroxysmal nocturnal hemoglobinuria
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DOI：
10.1182/blood.v87.6.2546.bloodjournal8762546
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发表时间：
1996-03-15
期刊：
影响因子：
20.3
通讯作者：
Parker, CJ
中科院分区：
文献类型：
--
作者：
Endo, M;Ware, RE;Parker, CJ
这些研究的目的是确定阵发性睡眠性血红蛋白尿症（PNH）表型嵌合的分子基础。从女性患者的T细胞克隆的分析揭示了四个不同的表型的糖基磷脂酰肌醇锚定蛋白（GPI-AP）的表面表达的基础上。当分析来自这些克隆的PIG-A（PNH中突变的基因）时，鉴定出四个离散的体细胞突变。异常T细胞克隆中X染色体失活的分析与多克隆性一致。总之，这些研究表明，表型嵌合是PNH的特征是基因型嵌合的结果，至少在这种情况下，PNH是一种多克隆而不是单克隆疾病。四个不同的体细胞突变存在于一个单一的病人表明，在条件下，易患PNH PIG-A可能是超变的。(C)1996年，美国血液学会。
The purpose of these studies was to determine the molecular basis of the phenotypic mosaicism that is a defining feature of paroxysmal nocturnal hemoglobinuria (PNH). Analysis of T cell clones from a female patient revealed four distinct phenotypes based on surface expression of glycosyl phosphatidylinositol-anchored proteins (GPI-AP). When PIG-A (the gene that is mutant in PNH) from these clones was analyzed, four discrete somatic mutations were identified. Analysis of X chromosomal inactivation among the abnormal T cell clones was consistent with polyclonality. Together, these studies demonstrate that the phenotypic mosaicism that is characteristic of PNH is a consequence of genotypic mosaicism and that, at least in this case, PNH is a polyclonal rather than a monoclonal disease. That four distinct somatic mutations were present in a single patient suggests that in conditions that predispose to PNH PIG-A may be hypermutable. (C) 1996 by The American Society of Hematology.