The pathophysiology of fragile x syndrome
- PMID: 17477822
- DOI: 10.1146/annurev.genom.8.080706.092249
The pathophysiology of fragile x syndrome
Abstract
Fragile X syndrome is the most common form of inherited mental retardation. The disorder is mainly caused by the expansion of the trinucleotide sequence CGG located in the 5' UTR of the FMR1 gene on the X chromosome. The abnormal expansion of this triplet leads to hypermethylation and consequent silencing of the FMR1 gene. Thus, the absence of the encoded protein (FMRP) is the basis for the phenotype. FMRP is a selective RNA-binding protein that associates with polyribosomes and acts as a negative regulator of translation. FMRP appears to play an important role in synaptic plasticity by regulating the synthesis of proteins encoded by certain mRNAs localized in the dendrite. An advancing understanding of the pathophysiology of this disorder has led to promising strategies for pharmacologic interventions.
Similar articles
-
The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain anatomy.Brain. 2004 Dec;127(Pt 12):2672-81. doi: 10.1093/brain/awh256. Epub 2004 Oct 13. Brain. 2004. PMID: 15483045
-
FMR1 CGG repeat lengths mediate different regulation of reporter gene expression in comparative transient and locus specific integration assays.Gene. 2011 Oct 15;486(1-2):15-22. doi: 10.1016/j.gene.2011.06.034. Epub 2011 Jul 13. Gene. 2011. PMID: 21767618
-
microRNAs and Fragile X Syndrome.Adv Exp Med Biol. 2015;888:107-21. doi: 10.1007/978-3-319-22671-2_7. Adv Exp Med Biol. 2015. PMID: 26663181
-
The Fragile X premutation: new insights and clinical consequences.Eur J Med Genet. 2006 Jan-Feb;49(1):1-8. doi: 10.1016/j.ejmg.2005.11.001. Epub 2005 Dec 5. Eur J Med Genet. 2006. PMID: 16473304 Review.
-
Understanding the molecular basis of fragile X syndrome.Hum Mol Genet. 2000 Apr 12;9(6):901-8. doi: 10.1093/hmg/9.6.901. Hum Mol Genet. 2000. PMID: 10767313 Review.
Cited by
-
Variable expression of MECP2, CDKL5, and FMR1 in the human brain: Implications for gene restorative therapies.Proc Natl Acad Sci U S A. 2024 Feb 27;121(9):e2312757121. doi: 10.1073/pnas.2312757121. Epub 2024 Feb 22. Proc Natl Acad Sci U S A. 2024. PMID: 38386709
-
Current Approaches to Epigenetic Therapy.Epigenomes. 2023 Sep 30;7(4):23. doi: 10.3390/epigenomes7040023. Epigenomes. 2023. PMID: 37873808 Free PMC article. Review.
-
Transcriptional Dysregulation and Impaired Neuronal Activity in FMR1 Knock-Out and Fragile X Patients' iPSC-Derived Models.Int J Mol Sci. 2023 Oct 5;24(19):14926. doi: 10.3390/ijms241914926. Int J Mol Sci. 2023. PMID: 37834379 Free PMC article.
-
Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes.Int J Mol Sci. 2023 Aug 6;24(15):12488. doi: 10.3390/ijms241512488. Int J Mol Sci. 2023. PMID: 37569863 Free PMC article. Review.
-
Chemogenetic manipulation of astrocyte activity at the synapse- a gateway to manage brain disease.Front Cell Dev Biol. 2023 Jul 18;11:1193130. doi: 10.3389/fcell.2023.1193130. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37534103 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical