Matijevic Tanja, Knezevic Jelena, Slavica Marko, Pavelic Jasminka
Rudjer Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia.
Eur Neurol. 2009;61(1):3-10. doi: 10.1159/000165342. Epub 2008 Oct 24.
Rett syndrome (RTT, MIM No. 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as an X-linked dominant trait, therefore almost exclusively affecting females. About 80% of RTT cases are sporadic caused by mutations in the MECP2 gene located on Xq28. The gene codes for two isoforms of the methyl-CpG-binding protein (MeCP2, MeCP2B) which are involved in transcriptional silencing through DNA methylation. The gene has 4 exons. The fourth one is the largest. Almost all mutations in MECP2 occur de novo. Although mutations are dispersed throughout the gene, about 67% of all MECP2 mutations, caused by C>T transitions at 8 CpG dinucleotides, are located in the third and fourth exon. The most common mutation is R168X. So far, there is no clear evidence on genotype-phenotype correlations. There are also reports claiming that the same mutation can provoke different phenotypes. It was shown that MeCP2 can silence certain genes. One of them, brain-derived neurotrophic factor, is essential for neural plasticity, learning and memory. This discovery revealed the role of MeCP2 in the control of neuronal activity-dependent gene regulation and suggested that the pathology of RTT may result from deregulation of this process.
瑞特综合征（RTT，MIM编号312750）是一种进行性神经发育障碍，也是智力发育迟缓最常见的病因之一。它以X连锁显性性状遗传，因此几乎只影响女性。约80%的RTT病例是由位于Xq28的MECP2基因突变引起的散发病例。该基因编码甲基化CpG结合蛋白的两种亚型（MeCP2、MeCP2B），它们通过DNA甲基化参与转录沉默。该基因有4个外显子。第四个外显子最大。MECP2基因的几乎所有突变都是新发的。尽管突变分散在整个基因中，但所有MECP2突变中约67%是由8个CpG二核苷酸处的C>T转换引起的，位于第三和第四外显子。最常见的突变是R168X。到目前为止，尚无关于基因型与表型相关性的明确证据。也有报道称相同的突变可引发不同的表型。研究表明，MeCP2可使某些基因沉默。其中之一是脑源性神经营养因子，它对神经可塑性、学习和记忆至关重要。这一发现揭示了MeCP2在控制神经元活动依赖性基因调控中的作用，并提示RTT的病理可能源于这一过程的失调。
