Phenobarbital use and neurological problems in FMR1 premutation carriers

Neurotoxicology. 2016 Mar:53:141-147. doi: 10.1016/j.neuro.2016.01.008. Epub 2016 Jan 21.

Abstract

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by a CGG expansion in the FMR1 gene located at Xq27.3. Patients with the premutation in FMR1 present specific clinical problems associated with the number of CGG repeats (55-200 CGG repeats). Premutation carriers have elevated FMR1 mRNA expression levels, which have been associated with neurotoxicity potentially causing neurodevelopmental problems or neurological problems associated with aging. However, cognitive impairments or neurological problems may also be related to increased vulnerability of premutation carriers to neurotoxicants, including phenobarbital. Here we present a study of three sisters with the premutation who were exposed differentially to phenobarbital therapy throughout their lives, allowing us to compare the neurological effects of this drug in these patients.

Keywords: FMR1; Fragile X; Neurotoxicity; Pesticides; Phenobarbital; Premutation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cognition Disorders / diagnostic imaging
  • Cognition Disorders / drug therapy
  • Cognition Disorders / genetics*
  • DNA Mutational Analysis
  • Excitatory Amino Acid Antagonists / therapeutic use*
  • Family Health
  • Female
  • Fragile X Mental Retardation Protein / genetics*
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Nervous System Diseases / diagnostic imaging
  • Nervous System Diseases / drug therapy
  • Nervous System Diseases / genetics*
  • Phenobarbital / therapeutic use
  • RNA, Messenger / metabolism
  • Trinucleotide Repeats / genetics*

Substances

  • Excitatory Amino Acid Antagonists
  • FMR1 protein, human
  • RNA, Messenger
  • Fragile X Mental Retardation Protein
  • Phenobarbital