Molecular Advances Leading to Treatment Implications for Fragile X Premutation Carriers

Details

• Alternative Title:
  Brain Disord Ther
• Personal Author:
  Polussa, Jonathan ; Schneider, Andrea ; Hagerman, Randi
• Description:
  Fragile X syndrome (FXS) is the most common single gene cause of intellectual disability and it is characterized by a CGG expansion of more than 200 repeats in the FMR1 gene, leading to methylation of the promoter and gene silencing. The fragile X premutation, characterized by a 55 to 200 CGG repeat expansion, causes health problems and developmental difficulties in some, but not all, carriers. The premutation causes primary ovarian insufficiency in approximately 20% of females, psychiatric problems (including depression and/or anxiety) in approximately 50% of carriers and a neurodegenerative disorder, the fragile X-associated tremor ataxia syndrome (FXTAS), in approximately 40% of males and 16% of females later in life. Recent clinical studies in premutation carriers have expanded the health problems that may be seen. Advances in the molecular pathogenesis of the premutation have shown significant mitochondrial dysfunction and oxidative stress in neurons which may be amenable to treatment. Here we review the clinical problems of carriers and treatment recommendations.
• Subjects:
  Aging Antioxidants Article FMR1 FMRP Fragile X Premutation FXTAS Oxidative Stress Treatment
• Source:
  Brain Disord Ther. 2014; 3.
• Pubmed ID:
  25436181
• Pubmed Central ID:
  PMC4245015
• Document Type:
  Journal Article
• Funding:
  R01 HD036071/HD/NICHD NIH HHS/United States ; R01 MH078041/MH/NIMH NIH HHS/United States ; U50 DD000596/DD/NCBDD CDC HHS/United States
• Volume:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:fc9292557f0eadfc96b29741d9608c61c778fe467fa03ad11ee5225e4dbdb856
• Download URL:
  https://stacks.cdc.gov/view/cdc/41998/cdc_41998_DS1.pdf
• File Type:
  [PDF - 873.60 KB ]