Abstract
Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat ( > 200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain.
Keywords: Fragile X, trinucleotide repeat, Prader-Willi phenotype, obesity, mGluR antagonists, GABA, intellectual disability, autism, cognitive impairments, post-pubertal macroorchidism
Current Genomics
Title: Fragile X Syndrome
Volume: 12 Issue: 3
Author(s): Yingratana McLennan, Jonathan Polussa, Flora Tassone and Randi Hagerman
Affiliation:
Keywords: Fragile X, trinucleotide repeat, Prader-Willi phenotype, obesity, mGluR antagonists, GABA, intellectual disability, autism, cognitive impairments, post-pubertal macroorchidism
Abstract: Recent data from a national survey highlighted a significant difference in obesity rates in young fragile X males (31%) compared to age matched controls (18%). Fragile X syndrome (FXS) is the most common cause of intellectual disability in males and the most common single gene cause of autism. This X-linked disorder is caused by an expansion of a trinucleotide CGG repeat ( > 200) on the promotor region of the fragile X mental retardation 1 gene (FMR1). As a result, the promotor region often becomes methylated which leads to a deficiency or absence of the FMR1 protein (FMRP). Common characteristics of FXS include mild to severe cognitive impairments in males but less severe cognitive impairment in females. Physical features of FXS include an elongated face, prominent ears, and post-pubertal macroorchidism. Severe obesity in full mutation males is often associated with the Prader-Willi phenotype (PWP) which includes hyperphagia, lack of satiation after meals, and hypogonadism or delayed puberty; however, there is no deletion at 15q11-q13 nor uniparental maternal disomy. Herein, we discuss the molecular mechanisms leading to FXS and the Prader-Willi phenotype with an emphasis on mouse FMR1 knockout studies that have shown the reversal of weight increase through mGluR antagonists. Finally, we review the current medications used in treatment of FXS including the atypical antipsychotics that can lead to weight gain and the research regarding the use of targeted treatments in FXS that will hopefully have a significantly beneficial effect on cognition and behavior without weight gain.
Export Options
About this article
Cite this article as:
McLennan Yingratana, Polussa Jonathan, Tassone Flora and Hagerman Randi, Fragile X Syndrome, Current Genomics 2011; 12 (3) . https://dx.doi.org/10.2174/138920211795677886
DOI https://dx.doi.org/10.2174/138920211795677886 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
Call for Papers in Thematic Issues
Current Genomics in Cardiovascular Research
Cardiovascular diseases are the main cause of death in the world, in recent years we have had important advances in the interaction between cardiovascular disease and genomics. In this Research Topic, we intend for researchers to present their results with a focus on basic, translational and clinical investigations associated with ...read more
Deep learning in Single Cell Analysis
The field of biology is undergoing a revolution in our ability to study individual cells at the molecular level, and to integrate data from multiple sources and modalities. This has been made possible by advances in technologies for single-cell sequencing, multi-omics profiling, spatial transcriptomics, and high-throughput imaging, as well as ...read more
New insights on Pediatric Tumors and Associated Cancer Predisposition Syndromes
Because of the broad spectrum of children cancer susceptibility, the diagnosis of cancer risk syndromes in children is rarely used in direct cancer treatment. The field of pediatric cancer genetics and genomics will only continue to expand as a result of increasing use of genetic testing tools. It's possible that ...read more
![](/images/wayfinder.jpg)
- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
- Announcements
Related Articles
-
Role of Central and Peripheral CRH in Skin
Current Molecular Pharmacology Human Recombinant Leptin Administration as a Potential Obesity Therapy
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) GABAergic Contributions to the Pathophysiology of Depression and the Mechanism of Antidepressant Action
CNS & Neurological Disorders - Drug Targets Influence of the Novelty-Seeking Endophenotype on the Rewarding Effects of Psychostimulant Drugs in Animal Models
Current Neuropharmacology Clinical Uses of Melatonin: Evaluation of Human Trials
Current Medicinal Chemistry New Targets for Treating the Underlying Pathophysiology and Nonmotor Aspects of Parkinson's Disease
CNS & Neurological Disorders - Drug Targets Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology
Current Medicinal Chemistry Neuronal Histamine and Histamine Receptors in Food Intake and Obesity
Mini-Reviews in Medicinal Chemistry Global Life-Long Health Benefits of Repression of Hypothalamic NPY System by Central Leptin Gene Therapy
Current Topics in Medicinal Chemistry Relaxin: New Functions for an Old Peptide
Current Protein & Peptide Science From Preclinical to Clinical Trials: An Update on Potential Therapies for Huntington’s Disease
Current Psychopharmacology The Role of the Calcium-Sensing Receptor in Human Pathophysiology
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Kisspeptin Mediated Signaling in Cancer
Current Topics in Medicinal Chemistry Impact of Dietary Fats on Brain Functions
Current Neuropharmacology Therapeutic Potential for Thyroid Hormone Receptor-β Selective Agonists for Treating Obesity, Hyperlipidemia and Diabetes
Current Vascular Pharmacology Neonatal Brain Hemorrhage (NBH) of Prematurity: Translational Mechanisms of the Vascular-Neural Network
Current Medicinal Chemistry Double-Edged Sword of Novel Anti-Cancer Treatment: Proteasome Inhibition in the Growth Plate Causes Impairment of Longitudinal Bone Growth
Current Pediatric Reviews Sleep and Antidepressant Treatment
Current Pharmaceutical Design Glia as a Turning Point in the Therapeutic Strategy of Parkinsons Disease
CNS & Neurological Disorders - Drug Targets Common Therapeutic Strategies in the Management of Sexual Dysfunction and Cardiovascular Disease
Current Drug Targets - Cardiovascular & Hematological Disorders