Fragilex Logo
Fragilex Canada Foundation

What is Fragile X ?

The term Fragile X refers to a group of conditions due to defects in a gene on the X chromosome:

  • Fragile X syndrome (FXS)
  • Fragile X-associated Tremor Ataxia Syndrome (FXTAS)
  • Fragile X-associated primary ovarian insufficiency (FXPOI)

Fragile X syndrome (FXS), first known as Martin-Bell syndrome, is the most common inherited form of mental impairment. FXS affects 1 in 4,000 boys and 1 in 6,000 girls of all races and ethnic groups. While Fragile X individuals have a normal life expectancy, most will need support and care for their entire lives.

A single gene in the brain cells shuts down, causing Fragile X syndrome. In 1991, scientists discovered the defect in a gene on the X chromosome (called FMR1) that causes FXS. In affected individuals, this gene is shut down and cannot manufacture the protein it normally makes – a protein vital for normal brain development and functioning.

Large-scale population studies of Fragile X still need to be done, but it is clear that this is one of the most common genetic diseases in humans. Most people with Fragile X are not yet correctly diagnosed.

Research is aimed at developing effective treatments. In addition, this research is leading to better understanding and treatments for other conditions, such as autism, and Alzheimer’s Disease.

Grant reports

2016

Principal Investigator: Dr. Karun K. Singh Ph.D. McMaster University, Stem Cell and Cancer Research Institute
Postdoctoral fellow: Dr. Sean White Ph.D
Amount: $45,000
Start Date: September 1, 2016

The Role of TAO2 in Fragile X

The underlying genetic cause of Fragile-X syndrome (FXS) is due to a failure in the production of the fragile X mental retardation protein (FMRP), through the silencing of the Fmr1 gene. In neurons, FMRP acts as repressor of protein production and is known to influence neurotransmitter release and synaptic plasticity. When FMRP is missing, the result is often an increase in protein levels involved in a number of pathways involved in learning and memory. Since it has been shown that FMRP can bind at least 842 different targets in the brain, it is difficult to distinguish the effect of one protein with another. Considering the high prevalence of autism spectrum disorders in FXS patients, it is not surprising that a number of FMRP binding targets are also autism-linked genes. One of these FMRP targets, whose function that we explore in our lab, is the enzyme known asthousand and one amino acid kinase 2 (TAO2). By comparing the brain cell profile of FXS mice, with a mouse deficient in only a single target (TAO2 for example), we can connect novel molecular pathways that contribute to effects of the fragile X mutation on affected individuals.  The similarities between the two models revolve around the impaired brain cell branches (dendritic spine morphology), which is the main site of excitatory synaptic transmission, and its underlying molecular pathways. These dendritic spines normally have a group of receptors on their surface, which are known as the metabotropic glutamate receptors (mGluR). The disruption of this pathway is currently the focus of potential therapeutic interventions. We hope to explore a novel FMRP-TAO2 pathway to determine if it is dependent on the activation of mGluR receptors, or possibly affected through an alternative mechanism, which may be an ultimate target for possible drug discovery.

Clicky