Abstract
CGG-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions ( > 200 CGG repeats) of the gene are generally silenced, resulting in absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation range (55-200 CGG repeats) result in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delay and autism. Thus, the FMR1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanisms, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represents a paradigm for understanding gene-brain relationships and the means by which diverse genetic mechanisms can give rise to a common behavioral phenotype.
Keywords: fragile X mental retardation 1 gene, Idiopathic Autism, methyl-CpG binding protein, Neuroimaging, CGG repeat
Current Pediatric Reviews
Title: The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments
Volume: 4 Issue: 1
Author(s): Randi J. Hagerman, Susan M. Rivera and Paul J. Hagerman
Affiliation:
Keywords: fragile X mental retardation 1 gene, Idiopathic Autism, methyl-CpG binding protein, Neuroimaging, CGG repeat
Abstract: CGG-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions ( > 200 CGG repeats) of the gene are generally silenced, resulting in absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation range (55-200 CGG repeats) result in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X-associated tremor/ataxia syndrome (FXTAS), and likely additional cases of developmental delay and autism. Thus, the FMR1 gene is causative of a common (autism) phenotype via two entirely different pathogenic mechanisms, RNA toxicity and gene silencing. The study of this gene and its pathogenic mechanisms therefore represents a paradigm for understanding gene-brain relationships and the means by which diverse genetic mechanisms can give rise to a common behavioral phenotype.
Export Options
About this article
Cite this article as:
Hagerman J. Randi, Rivera M. Susan and Hagerman J. Paul, The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments, Current Pediatric Reviews 2008; 4 (1) . https://dx.doi.org/10.2174/157339608783565770
DOI https://dx.doi.org/10.2174/157339608783565770 |
Print ISSN 1573-3963 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6336 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Sodium Channel Inhibitor Drug Discovery Using Automated High Throughput Electrophysiology Platforms
Combinatorial Chemistry & High Throughput Screening Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Current Cancer Drug Targets Vascular Endothelial Growth Factor Receptors [VEGFR] as Target in Breast Cancer Treatment: Current Status in Preclinical and Clinical Studies and Future Directions
Current Topics in Medicinal Chemistry Cognitive - Behavioral Therapy in Central Sensitivity Syndromes
Current Rheumatology Reviews Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives
Current Pharmaceutical Design Mechanisms Involved in Metformin Action in the Treatment of Polycystic Ovary Syndrome
Current Pharmaceutical Design Fluid Retention and Rostral Fluid Shift in Sleep-Disordered Breathing
Current Hypertension Reviews Celiac Disease: An Emerging Epidemic
Current Nutrition & Food Science Cachexia and Herbal Medicine: Perspective
Current Pharmaceutical Design Insights into the Role of Matrix Metalloproteinases and Tissue Inhibitor of Metalloproteinases in Health and Disease
Current Chemical Biology Animal Models of Depressive Illness: The Importance of Chronic Drug Treatment
Current Pharmaceutical Design Resveratrol and Stroke: from Chemistry to Medicine
Current Neurovascular Research Vascular Disease and Insulin-Like Growth Factor-1
Vascular Disease Prevention (Discontinued) Mutant B-Raf Kinase Inhibitors as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Application of RNA Interference for the Control of Female Reproductive Functions
Current Pharmaceutical Design Psychosocial Factors and Central Sensitivity Syndromes
Current Rheumatology Reviews Computational and Experimental Approaches for Modeling Gene Regulatory Networks
Current Pharmaceutical Design CD4-Induced Epitopes in the HIV Envelope Glycoprotein, Gp120
Current HIV Research Medicinal Chemistry of Antimigraine Drugs
Current Medicinal Chemistry Drug Therapy of Neuropathic Pain: Current Developments and Future Perspectives
Current Drug Targets