RUBINSTEIN-TAYBI SYNDROME CAUSED BY MUTATIONS IN THE TRANSCRIPTIONAL COACTIVATOR CBP
RUBINSTEIN-TAYBI SYNDROME CAUSED BY MUTATIONS IN THE TRANSCRIPTIONAL COACTIVATOR CBP
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DOI：
10.1038/376348a0
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发表时间：
1995-07-27
期刊：
影响因子：
64.8
通讯作者：
BREUNING, MH
中科院分区：
文献类型：
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作者：
PETRIJ, F;GILES, RH;BREUNING, MH
Rubinstein-Taybi综合征（RTS）是一种定义明确的综合征，以面部异常、拇指宽大、大脚趾宽大和智力迟钝为主要临床特征（1-3）。许多RTS患者在16p13.3染色体上存在断点和微缺失（参考文献4-8）。在这里，我们报道所有这些断点都局限于包含人类CREB结合蛋白（CBP）基因的区域，CBP是参与环amp调节基因表达的核蛋白共激活因子（9-12）。我们发现RTS不仅源于16p染色体的总体重排，还源于CBP基因本身的点突变。由于患者的突变是杂合的，我们认为CBP基因的一个功能拷贝的丢失是RTS发育异常的基础，可能是恶性肿瘤的倾向。
THE Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features(1-3). Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating co-activator in cyclic-AMP-regulated gene expression(9-12). We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.