New Perspectives on the Biology of Fragile X Syndrome

• Type of Material: Article
• Authors: Tao Wang, Emory University; Steven M. Bray, Emory University; Stephen T. Warren, Emory University
• Language: English
• Date: 2012-06
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.gde.2012.02.002
• Title of Journal or Parent Work: Current Opinion in Genetics and Development
• ISSN: 0959-437X
• Volume: 22
• Issue: 3
• Start Page: 256
• End Page: 263
• Grant/Funding Information: This work is supported by the NIH grant HD020521 and HD024064.
• Keywords: intellectual disability (ID); translational regulation; microRNAs; ribosomal stalling; long term depression (LTD); missense mutation; group 1 metabotropic glutamate receptors; adult neurogenesis; human embryonic stem cell (hESC); induced pluripotent stem cell (iPS); presynapse; fragile X syndrome
• Research Categories: Biology, Genetics

Abstract

Fragile X syndrome (FXS) is a trinucleotide repeat disorder caused by a CGG repeat expansion in FMR1, and loss of its protein product FMRP. Recent studies have provided increased support for the role of FMRP in translational repression via ribosomal stalling and the microRNA pathway. In neurons, particular focus has been placed on identifying the signaling pathways such as PI3K and mTOR downstream of group 1 metabotropic glutamate receptors (mGluR1/5) that regulate FMRP. New evidence also suggests that loss of FMRP causes presynaptic dysfunction and abnormal adult neurogenesis. In addition, studies on FXS stem cells especially induced pluripotent stem (iPS) cells and new sequencing efforts hold out promise for deeper understanding of the silencing process and mutation spectrum of FMR1.