MECP2 and beyond: phenotype-genotype correlations in Rett syndrome.
The association of Rett syndrome with pathogenic mutations of the methyl-CpG binding protein 2 (MECP2) gene was first made in 1999. Since that time, it has been found that the clinical phenotype can, at least in part, be explained in terms of the type and location of the MECP2 mutation and epigenetic factors such as skewing of X-chromosome inactivation. In addition, MECP2 mutations may be associated with non-Rett syndrome clinical phenotypes, including nonsyndromic and syndromic X-linked mental retardation and Angelman-like phenotypes. Intense research efforts are currently focused on understanding the pathogenesis of Rett syndrome, using sophisticated techniques such as microarray analysis, and the development of mouse models, with an ultimate aim being the development of targeted therapies that could ameliorate or even prevent the devastating consequences of this enigmatic neurodevelopmental disorder.
Christodoulou
John
J
Western Sydney Genetics Program, The Children's Hospital at Westmead, NSW, Australia. johnc@chw.edu.au
Weaving
Linda S
LS
D017204:Angelman Syndrome / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D004303:Dosage Compensation, Genetic; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D005838:Genotype; D006801:Humans; D038901:X-Linked Intellectual Disability / Q000235:genetics / Q000503:physiopathology; D051783:Methyl-CpG-Binding Protein 2; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012097:Repressor Proteins; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D012097:Repressor Proteins