CARRIER DETECTION IN X-LINKED AGAMMAGLOBULINEMIA BY ANALYSIS OF X-CHROMOSOME INACTIVATION
CARRIER DETECTION IN X-LINKED AGAMMAGLOBULINEMIA BY ANALYSIS OF X-CHROMOSOME INACTIVATION
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DOI：
10.1056/nejm198702193160802
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发表时间：
1987-02-19
影响因子：
158.5
通讯作者：
VOGELSTEIN, B
中科院分区：
文献类型：
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作者：
FEARON, ER;WINKELSTEIN, JA;VOGELSTEIN, B
我们使用最近开发的策略来分析人类细胞群中X染色体失活的模式，以研究X连锁无丙种球蛋白血症家族的女性成员，即，以检测携带者状态并检验该疾病是由B细胞发育中的内在缺陷引起的假设。根据这一策略，重组DNA探针同时检测限制性片段长度多态性和X染色体基因甲基化模式。随机X-失活模式中观察到孤立的外周血粒细胞，T淋巴细胞，和B淋巴细胞的妇女谁不是携带者。相反，两条X染色体中的一条优先在三个疾病携带者的外周B细胞中活跃，而不是T细胞或粒细胞。这一观察结果有力地支持了X连锁无丙种球蛋白血症由B细胞发育的内在缺陷引起的假设。此外，本文所述的分析可用于直接鉴定该疾病家族中的携带者。
We used a recently developed strategy to analyze patterns of X-chromosome inactivation in human cell populations in order to study female members of families with X-linked agammaglobulinemia-i.e., to detect the carrier state and to test the hypothesis that the disorder results from a defect intrinsic in the development of B cells. According to this strategy, recombinant-DNA probes simultaneously detect restriction-fragment-length polymorphisms and patterns of methylation of X-chromosome genes. Random X-inactivation patterns were observed in isolated peripheral-blood granulocytes, T lymphocytes, and B lymphocytes of women who were not carriers. In contrast, one of the two X chromosomes was preferentially active in the peripheral B cells, but not the T cells or granulocytes, of three carriers of the disorder. This observation strongly supports the hypothesis that X-linked agammaglobulinemia results from an intrinsic defect in B-cell development. Moreover, the analysis described here can be used for direct identification of carriers in families with this disease.