Roelfsema Jeroen H, Peters Dorien J M
Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Expert Rev Mol Med. 2007 Aug 20;9(23):1-16. doi: 10.1017/S1462399407000415.
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.
鲁宾斯坦-泰比综合征的特征为智力发育迟缓、生长发育迟缓以及特殊的面部畸形。该综合征较为罕见，在每10万名新生儿中约有1例患者。已确定两个基因——CREBBP和EP300——的突变会导致该综合征。这两个基因具有很强的同源性，并编码组蛋白乙酰转移酶（HATs），这些酶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鲁宾斯坦-泰比综合征患者中出现的现象。尽管在CREBBP中发现的一些突变是易位、倒位和大片段缺失，但大多数是点突变或小片段缺失和插入。EP300中的突变相对较少。对患者的广泛筛查显示，约50%的病例中存在CREBBP和EP300的突变。其余患者综合征的病因仍有待确定，但其他基因也可能参与其中。在此，我们描述鲁宾斯坦-泰比综合征的临床表现，回顾突变谱，并讨论目前对致病分子机制的理解。
