Rubinstein-Taybi syndrome: clinical and molecular overview
Rubinstein-Taybi syndrome: clinical and molecular overview
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DOI：
10.1017/s1462399407000415
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发表时间：
2007-08-20
影响因子：
6.2
通讯作者：
Peters, Dorien J. M.
中科院分区：
文献类型：
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作者：
Roelfsema, Jeroen H.;Peters, Dorien J. M.
Rubinstein-Taybi 综合征的特征是智力低下、生长迟缓和特殊的畸形。该综合征十分罕见，发病率约为 10 万名新生儿中就有 1 人患病。两个基因（CREBBP 和 EP300）的突变已被确定是导致该综合征的原因。这两个基因表现出很强的同源性，并编码组蛋白乙酰转移酶（HAT），这是参与许多信号通路的转录共激活因子。 HAT 活性的丧失足以解释 Rubinstein-Taybi 患者中所见的现象。虽然CREBBP中发现的一些突变是易位、倒位和大缺失，但大多数是点突变或小缺失和插入。 EP300 的突变相对罕见。对患者的广泛筛查发现，约 50% 的病例存在 CREBBP 和 EP300 突变。其余患者出现该综合征的原因仍有待确定，但也可能涉及其他基因。在这里，我们描述了 Rubinstein-Taybi 综合征的临床表现，回顾了突变谱并讨论了目前对致病分子机制的理解。
Rubinstein-Taybi syndrome is characterised by mental retardation, growth retardation and a particular dysmorphology. The syndrome is rare, with a frequency of approximately one affected individual in 100 000 newborns. Mutations in two genes - CREBBP and EP300 - have been identified to cause the syndrome. These two genes show strong homology and encode histone acetyltransferases (HATs), which are transcriptional co-activators involved in many signalling pathways. Loss of HAT activity is sufficient to account for the phenomena seen in Rubinstein-Taybi patients. Although some mutations found in CREBBP are translocations, inversions and large deletions, most are point mutations or small deletions and insertions. Mutations in EP300 are comparatively rare. Extensive screening of patients has revealed mutations in CREBBP and EP300 in around 50% of cases. The cause of the syndrome in the remaining patients remains to be identified, but other genes could also be involved. Here, we describe the clinical presentation of Rubinstein-Taybi syndrome, review the mutation spectrum and discuss the current understanding of causative molecular mechanisms.