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A Robust Polymerase Chain Reaction-based Assay for Quantifying Cytosine-guanine-guanine Trinucleotide Repeats in Fragile X Mental Retardation-1 Gene
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Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism

D Z Loesch1, M S Khaniani, H R Slater

  • 1School of Psychological Science, La Trobe University, Melbourne/Bundoora, Victoria, Australia. d.loesch@latrobe.edu.au

Clinical Genetics
|October 3, 2009
PubMed

Insights

Fragile X-associated tremor/ataxia syndrome (FXTAS) is linked to FMR1 gene premutation alleles. This study found that both premutation and smaller "grey zone" FMR1 alleles are more common in males with parkinsonism, suggesting a role in the condition's development.

Area of Science:

  • Neurogenetics
  • Movement Disorders

Background:

  • Fragile X-associated tremor/ataxia syndrome (FXTAS) is associated with FMR1 gene premutation alleles (55-200 CGG repeats).
  • Neurological issues in FXTAS are linked to toxic gain-of-function from excessive FMR1 messenger RNA (mRNA).
  • Elevated FMR1 mRNA levels are also observed in carriers of smaller expansion
  • grey zone
  • alleles (40-54 CGGs).

Purpose of the Study:

  • To investigate the potential role of FMR1 premutation and grey zone alleles in the etiology of parkinsonism.
  • To determine if these alleles are more prevalent in males diagnosed with idiopathic Parkinson's disease or other parkinsonian disorders.

Main Methods:

  • Screening of 228 Australian males with parkinsonism for FMR1 premutation and grey zone alleles.
  • Comparison of allele frequencies in cases against a population-based control group (578 Tasmanian male newborns).
  • Statistical analysis using Fisher's exact test and calculation of odds ratios (OR) with 95% confidence intervals (CI).

Main Results:

  • A significant excess of FMR1 premutation carriers was found in the parkinsonism group (p = 0.006).
  • A more than twofold increase in grey zone allele carriers was observed in the combined case sample (OR = 2.36, 95% CI: 1.20-4.63).
  • This increase in grey zone carriers was also significant in Tasmanian cases only (OR = 2.33, 95% CI: 1.06-5.13).

Conclusions:

  • FMR1 premutation alleles are significantly associated with parkinsonism.
  • FMR1 grey zone alleles may also contribute to the development of parkinsonism.
  • These findings suggest a potential genetic link between FMR1 expansions and movement disorders like Parkinson's disease.

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