Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2
- R. Amir, I. V. D. Veyver, Mimi Wan, C. Q. Tran, U. Francke, H. Zoghbi
- BiologyNature Genetics
- 1 October 1999
This study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
It is shown that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target, and that it can function as both an activator and a repressor of transcription.
Towards a proteome-scale map of the human protein–protein interaction network
An initial version of a proteome-scale map of human binary protein–protein interactions is described, which increases by ∼70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins.
Math1 Expression Redefines the Rhombic Lip Derivatives and Reveals Novel Lineages within the Brainstem and Cerebellum
Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation.
- R. Allen, H. Zoghbi, A. Moseley, H. Rosenblatt, J. Belmont
- BiologyAmerican Journal of Human Genetics
The human androgen-receptor gene (HUMARA) contains a highly polymorphic trinucleotide repeat in the first exon that correlates with X inactivation, and the development of a PCR assay that distinguishes between the maternal and paternal alleles and identifies their methylation status is developed.
Trinucleotide repeat disorders.
It is exciting that within a span of 15 years, pathogenesis studies of this class of disorders are beginning to reveal pathways that are potential therapeutic targets.
Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channel
It is concluded that a small polyglutamine expansion in the human α1A calcium channel is most likely the cause of a newly classified autosomal dominant spinocerebellar ataxia, SCA6.
Mild overexpression of MeCP2 causes a progressive neurological disorder in mice.
The data demonstrate that MeCP2 levels must be tightly regulated in vivo, and that even mild overexpression of this protein is detrimental, and support the possibility that duplications or gain-of-function mutations in MECP2 might underlie some cases of X-linked delayed-onset neurobehavioral disorders.
Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation.
The data suggest that MeCP2 may become abundant only once a neuron has reached a certain degree of maturity, and that this may explain some aspects of the RTT phenotype.
Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1
There is a direct correlation between the size of the (CAG)n repeat expansion and the age–of–onset of SCA1, with larger alleles occurring in juvenile cases.