The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments

@article{Hagerman2008TheFX,
  title={The Fragile X Family of Disorders: A Model for Autism and Targeted Treatments},
  author={Randi J. Hagerman and Susan M. Rivera and Susan M. Rivera and Paul J. Hagerman},
  journal={Current Pediatric Reviews},
  year={2008},
  volume={4},
  pages={40-52}
}
CGG-repeat expansion mutations of the fragile X mental retardation 1 (FMR1) gene are the leading known cause of autism and autism spectrum disorders (ASD). Full mutation expansions (>200 CGG repeats) of the gene are gen- erally silenced, resulting in absence of the FMR1 protein and fragile X syndrome. By contrast, smaller expansions in the premutation range (55-200 CGG repeats) result in excess gene activity and RNA toxicity, which is responsible for the neurodegenerative disorder, fragile X… 
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A screening study of the cohort from CHARGE, a large-scale, population-based, case control study, identifies six subjects carrying an expanded allele of fragile X syndrome, which emphasize the importance of screening for FXS in a population with intellectual disabilities and ASD.
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Over the past 2 decades, scientists have made significant advancements in identifying and describing genetic, molecular, and cellular underpinnings of FXS, allowing for a more precise diagnosis of this condition.
Broad clinical involvement in a family affected by the fragile X premutation.
TLDR
This is the first case report that demonstrates only premutation involvement across 3 generations, and it is hoped that this knowledge will facilitate the integration of this knowledge into clinical practice.
Early identification of autism in fragile X syndrome: a review.
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  • 2013
TLDR
Studying the emergence and stability of autism in infants with FXS has multiple benefits such as clarifying the underlying mechanisms of the development of Autism in FXS and solidifying similarities and differences between co-morbid FXS with autism and IA.
Advances in the Treatment of Fragile X Syndrome
The FMR1 mutations can cause a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socioemotional problems, in individuals with the full…
Screening for FMR1 CGG Repeat Expansion in Thai Patients with Autism Spectrum Disorder
TLDR
It is indicated that CGG repeat expansions of the FMR1 gene may not be a common genetic cause of nonsyndromic ASD in Thai patients, and further studies for mutations other than the CGG expansion in the F MR1 gene are required to get a better information on FXS prevalence.
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References

SHOWING 1-10 OF 195 REFERENCES
Lessons from Fragile X Regarding Neurobiology, Autism, and Neurodegeneration
  • R. Hagerman
  • Biology
    Journal of developmental and behavioral pediatrics : JDBP
  • 2006
TLDR
The fragile X mental retardation 1 gene (FMR1) mutation causes two disorders: fragile X syndrome and the fragile X-associated tremor/ataxia syndrome (FXTAS), which are described in detail.
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1
Autism Spectrum Disorders and Attention-Deficit/Hyperactivity Disorder in Boys with the Fragile X Premutation
TLDR
It is suggested that premutation carriers, even those who do not present clinically, may be at increased risk for an ASD and/or symptoms of ADHD and the use of psychotropic medications was significantly higher in probands with the premutation compared with that in controls.
FMR1 and the fragile X syndrome: Human genome epidemiology review
TLDR
The relatively high prevalence of the premutation and full mutation genotypes coupled with technological advances in genetic testing make the fragile X syndrome amenable to screening.
Differential impact of the FMR1 gene on visual processing in fragile X syndrome.
TLDR
Findings provide the first evidence that the loss of a single gene product, FMRP, in humans leads to abnormal neuroanatomical morphology of the LGN and a concomitant selective visual deficit of the M pathway.
Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS).
TLDR
The most striking finding is the highly significant association between the number of CGG repeats and the numbers of intranuclear inclusions in both neurons and astrocytes, indicating that the CGG repeat is a powerful predictor of neurological involvement in males, both clinically (age of death) and neuropathologically (number of inclusions).
Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population.
TLDR
It is demonstrated that older male carriers of premutation alleles of the FMR1 gene are at high risk of developing fragile X-associated tremor/ataxia syndrome (FXTAS), and older men with ataxia and intention tremor should be screened for the F MR1 mutation.
Amygdala dysfunction in men with the fragile X premutation.
TLDR
The reduced amygdala activation in the FMR1 premutation group was significantly associated with self-report of psychological symptoms on the Symptom Checklist-90--Revised, and may be related to social cognition deficits reported previously in children and adults with the premutation.
Suppression of two major Fragile X Syndrome mouse model phenotypes by the mGluR5 antagonist MPEP
Autism and cytogenetic abnormalities: Solving autism one chromosome at a time
TLDR
Powerful new methods for identifying novel regions of the genome causing or contributing to autism also will be discussed and will start to explain the etiology for some percentage of the remaining 85% to 90% of autism cases.
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