engleski

RETT syndrome: from gene to the disease

Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation. It is transmitted as X-linked dominant trait, therefore almost exclusively affecting females. About 80% of Rett cases are sporadic caused by mutations in MECP2 gene located on Xq28. The gene codes for two isoforms of 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 eight 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 correlation. There are also the reports that the same mutation can provoke different phenotypes. It was shown that MeCP2 can silence certain genes. One of them, BDNF, 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.

MECP2 gene ; neurodevelopmental disorder ; Rett syndrome

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