Molecular biomarkers in fragile x syndrome

Marwa Zafarullah, Flora Tassone

Research output: Contribution to journalArticle

Abstract

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and a known monogenic cause of autism spectrum disorder (ASD). It is a trinucleotide repeat disorder, in which more than 200 CGG repeats in the 5’ untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded fragile X mental retardation 1 protein, FMRP. FMRP is an RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity, seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular biomarkers for identifying potential targets for therapies. In this paper, we review candidate molecular biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.

Original languageEnglish (US)
Article number96
JournalBrain Sciences
Volume9
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Fragile X Syndrome
Biomarkers
Intellectual Disability
Fragile X Mental Retardation Protein
Clinical Trials
Trinucleotide Repeats
Neuronal Plasticity
RNA-Binding Proteins
5' Untranslated Regions
Protein Biosynthesis
Gene Silencing
Methylation
Seizures
Language
Anxiety
Animal Models
Maintenance
Therapeutics
Genes
Proteins

Keywords

  • ASD
  • FMR1
  • Fmr1 KO mouse
  • FMRP
  • Fragile X syndrome
  • Intellectual disability
  • Molecular biomarkers

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Molecular biomarkers in fragile x syndrome. / Zafarullah, Marwa; Tassone, Flora.

In: Brain Sciences, Vol. 9, No. 5, 96, 01.05.2019.

Research output: Contribution to journalArticle

Zafarullah, Marwa ; Tassone, Flora. / Molecular biomarkers in fragile x syndrome. In: Brain Sciences. 2019 ; Vol. 9, No. 5.
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