Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency.
Molecular analysis of X-linked agammaglobulinemia with growth hormone deficiency.
复制标题
X连锁无丙种球蛋白血症伴生长激素缺乏的分子分析。
DOI：
10.1016/s0022-3476(05)82051-7
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Puck,JM
中科院分区：
文献类型：
--
作者：
Conley,ME;Burks,AW;Herrod,HG;Puck,JM
为了解决导致X连锁低grammagloblinemia（分离生长激素缺乏症）综合征的基因（或多个基因）与负责典型X连锁agammagloblinemia （XLA）的基因之间的关系，我们使用了细胞遗传学，检查该缺陷的潜在携带者的X染色体失活模式，并进行连锁分析，研究两个不相关的家族，其中受影响的男性有分离的生长激素缺乏症，免疫表现与典型的XLA难以区分。g带核型和中期染色体的流式细胞分析均不能证明两个家族中存在缺失。对X失活的研究表明，来自两个家庭的患病男孩的母亲在B细胞中选择性地使用单个X染色体作为活跃的X染色体，而不是T细胞。这种模式与在典型XLA的专用载体中看到的模式相同。连锁分析表明，该基因（或多个基因）最有可能位于DXS3和DXS94之间X染色体长臂的中间部分。X染色体的这一部分约占X染色体总数的5%，包含XLA基因。这些发现与XLA和生长激素缺乏症的结合是一致的，这种结合是由涉及XLA基因或典型XLA基因的等位基因变异的小的、连续的基因缺失综合征引起的。
To address the relationship between the gene (or genes) that causes the syndrome of X-linked hypogrammaglobulinemia with isolated growth hormone deficiency and the gene responsible for typical X-linked agammaglobulinemia (XLA), we have used cytogenetics, examination of X chromesome inactivation patterns in potential carriers of the defect, and linkage analysis to study two unrelated families in which the affected males had isolated growth hormone deficiency and immunologic findings indistinguishable from those of typical XLA. A deletion could not be demonstrated in either family by G-banded karyotypes or flow cytometric analysis of metaphase chromosomes. Studies of X inactivation showed that mothers of affected boys from both families exhibited selective use of a single X chromosome as the active X chromosome in B cells but not T cells. This pattern is the same as that seen in obligate carriers of typical XLA. Linkage analysis demonstrated the most likely location for this gene (or genes) to be the midportion of the long arm of the X chromosome between DXS3 and DXS94. This segment of the X chromosome, which constitutes approximately 5% of the total X chromosome, encompasses the gene for XLA. These findings are consistent with the combination of XLA and growth hormone deficiency being caused by a small, contiguous, gene deletion syndrome involving the gene for XLA or an allelic variant of the gene for typical XLA.