Stewart D M, Notarangelo L D, Kurman C C, Staudt L M, Nelson D L
Immunophysiology Section, National Cancer Institutes of Health, Bethesda, MD 20892, USA.
J Immunol. 1995 Sep 1;155(5):2770-4.
In 1980 the clinical syndrome of X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLA/GHD) was described. XLA/GHD patients have reduced serum levels of Ig and normal cell-mediated immunity, and thus resemble patients with Bruton's X-linked agammaglobulinemia (XLA). However, XLA/GHD patients also have isolated GHD. Mutations and deletions in the Bruton's tyrosine kinase gene (BTK) are responsible for Bruton's XLA. We investigated BTK gene expression in an XLA/GHD patient from the family originally described by Northern analysis, cDNA sequencing, and Western analysis of protein production using mAb to BTK. BTK mRNA was normal in size and abundance, and the mRNA sequence was normal over the coding region, except for a single silent mutation. BTK protein was present in normal amounts in PBMC of this patient. Thus, at the molecular level, XLA/GHD is a different disease entity from Bruton's XLA. These results suggest that undescribed genes critical for B cell development and growth hormone production exist on the X chromosome.
1980年，X连锁低丙种球蛋白血症与孤立性生长激素缺乏症（XLA/GHD）的临床综合征被描述。XLA/GHD患者血清免疫球蛋白水平降低，细胞介导免疫正常，因此与布鲁顿X连锁无丙种球蛋白血症（XLA）患者相似。然而，XLA/GHD患者还存在孤立性生长激素缺乏。布鲁顿酪氨酸激酶基因（BTK）的突变和缺失是导致布鲁顿XLA的原因。我们通过Northern分析、cDNA测序以及使用抗BTK单克隆抗体对蛋白质产生进行Western分析，研究了最初报道的家族中一名XLA/GHD患者的BTK基因表达。BTK mRNA的大小和丰度正常，除了一个单一的沉默突变外，编码区的mRNA序列正常。该患者外周血单核细胞中BTK蛋白含量正常。因此，在分子水平上，XLA/GHD是一种与布鲁顿XLA不同的疾病实体。这些结果表明，X染色体上存在对B细胞发育和生长激素产生至关重要的未描述基因。
