Review

Rett Syndrome: From the Gene to the Disease
Tanja Matijevic, Jelena Knezevic, Marko Slavica, Jasminka Pavelic

Rudjer Boskovic Institute, Division of Molecular Medicine, Zagreb, Croatia

Address of Corresponding Author

Eur Neurol 2009;61:3-10 (DOI: 10.1159/000165342)

  Key Words

• MECP2 gene
• Neurodevelopmental disorder
• Rett syndrome

  Abstract

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.

Copyright © 2008 S. Karger AG, Basel

  Author Contacts

Prof. Dr. Jasminka Pavelic
Rudjer Boskovic Institute, Division of Molecular Medicine, Laboratory of Molecular Oncology, Bijenicka 54
HR-10002 Zagreb (Croatia)
Tel. +385 1 4560 926, Fax +385 1 456 1010, E-Mail jpavelic@irb.hr

  Article Information

Received: February 1, 2008
Accepted: April 14, 2008
Published online: October 24, 2008
Number of Print Pages : 8
Number of Figures : 3, Number of Tables : 1, Number of References : 62