Conley M E, Puck J M
Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, PA 19104.
J Pediatr. 1988 May;112(5):688-94. doi: 10.1016/s0022-3476(88)80683-8.
We have recently demonstrated that B cells from obligate carriers of typical X-linked agammaglobulinemia (XLA) exhibit nonrandom X chromosome inactivation. The active X is always the X that does not carry the gene defect. To determine if this were also true in carriers of atypical XLA and to provide carrier detection for all women at risk of being carriers of XLA, we developed a technique that permits analysis of X chromosome inactivation in cells from any woman. This technique combines the production of somatic cell hybrids that selectively retain the active X chromosome with the use of X-linked restriction fragment length polymorphisms that permit the distinction of the two X chromosomes. Three obligate carriers of typical XLA and four women whose sons might be considered to have atypical or sporadic XLA were studied. B cell hybrids from all seven women demonstrated exclusive use a single X as the active X. In addition, B cell hybrids from four of eight women at 25% or 50% risk of being carriers exhibited nonrandom X chromosome inactivation, indicating that these women were also carriers of X-linked forms of hypogammaglobulinemia. These results illustrate a technique that can be used both to help define XLA and to provide carrier detection for all women at risk of being carriers of this disorder.
我们最近证明，典型X连锁无丙种球蛋白血症（XLA）的 obligate 携带者的B细胞表现出非随机的X染色体失活。活跃的X总是不携带基因缺陷的那条X染色体。为了确定这在非典型XLA携带者中是否也成立，并为所有有风险成为XLA携带者的女性提供携带者检测，我们开发了一种技术，该技术允许分析任何女性细胞中的X染色体失活情况。这项技术将选择性保留活跃X染色体的体细胞杂种的产生与使用X连锁限制性片段长度多态性相结合，后者能够区分两条X染色体。对3名典型XLA的 obligate 携带者和4名儿子可能被认为患有非典型或散发性XLA的女性进行了研究。来自所有7名女性的B细胞杂种均显示仅使用一条X作为活跃X染色体。此外，在有25%或50%携带者风险的8名女性中，有4名女性的B细胞杂种表现出非随机的X染色体失活，这表明这些女性也是X连锁型低丙种球蛋白血症的携带者。这些结果说明了一种既可以用于帮助定义XLA，又可以为所有有风险成为该疾病携带者的女性提供携带者检测的技术。
