CARRIER DETECTION IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY BASED ON PATTERNS OF X-CHROMOSOME INACTIVATION
CARRIER DETECTION IN X-LINKED SEVERE COMBINED IMMUNODEFICIENCY BASED ON PATTERNS OF X-CHROMOSOME INACTIVATION
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DOI：
10.1172/jci112967
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发表时间：
1987-05-01
影响因子：
15.9
通讯作者：
CONLEY, ME
中科院分区：
文献类型：
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作者：
PUCK, JM;NUSSBAUM, RL;CONLEY, ME
X 连锁形式的水联合免疫缺陷 (XSCID) 的诊断不足，因为尚无可用于检测携带者的方法。尽管患有 XSCID 的男孩缺乏 T 细胞，但女性携带者的免疫功能正常。如果携带者的所有 T 细胞均源自携带 XSCID 突变的 X 染色体在胚胎发生早期失活的前体，则可以预期携带者具有正常的免疫功能。利用体细胞杂交分离活性和非活性X染色体以及限制性片段长度多态性来区分它们，我们确定了XSCID携带者及其女性亲属的淋巴细胞X失活模式。在三个携带者的 T 细胞中，携带 XSCID 突变的 X 染色体始终处于不活跃状态。在一名高危女性的 T 细胞中也发现了非随机 X 失活，而另外两名女性的 T 细胞则具有正常的随机 X 失活。该方法构成了普遍适用的 XSCID 载体测试。
The X-linked form of water combined immunodeficiency (XSCID) is underdiagnosed because no methods have been available for detecting carriers. Although boys with XSCID are deficient in T cells, female carriers are immunologically normal. Carriers'' normal immune function would be expected if all their T cells were derived from precursors whose X chromosome bearing the XSCID mutation was inactivated early in embryogenesis. Using somatic cell hybridization to separate the active and inactive X chromosome and restriction fragment length polymorphisms to distinguish them, we have determined the lymphocyte X inactivation pattern in XSCID carriers and their female relatives. In the T cells of three carriers, the X chromosome bearing the XSCID mutation was consistently inactive. Nonrandom X inactivation was also found in the T cells of one at-risk female, while two others had normal, random X inactivation. This method constitutes a generally applicable carrier test for XSCID.