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. 2009 Nov;76(5):471-6.
doi: 10.1111/j.1399-0004.2009.01275.x. Epub 2009 Sep 30.

Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism

D Z Loesch  1 , M S Khaniani, H R Slater, J P Rubio, Q M Bui, K Kotschet, W D'Souza, A Venn, P Kalitsis, A K H Choo, T Burgess, L Johnson, A Evans, M Horne
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Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism

D Z Loesch et al. Clin Genet. 2009 Nov.

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) affects older males carrying premutation, that is, expansions of the CGG repeat (in the 55-200 range), in the FMR1 gene. The neurological changes are linked to the excessive FMR1 messenger RNA (mRNA), becoming toxic through a 'gain-of-function'. Because elevated levels of this mRNA are also found in carriers of the smaller expansion (grey zone) alleles, ranging from 40 to 54 CGGs, we tested for a possible role of these alleles in the origin of movement disorders associated with tremor. We screened 228 Australian males affected with idiopathic Parkinson's disease and other causes of parkinsonism recruited from Victoria and Tasmania for premutation and grey zone alleles. The frequencies of either of these alleles were compared with the frequencies in a population-based sample of 578 Guthrie spots from consecutive Tasmanian male newborns (controls). There was a significant excess of premutation carriers (Fisher's exact test p = 0.006). There was also a more than twofold increase in grey zone carriers in the combined sample of the Victorian and Tasmanian cases, with odds ratio (OR ) = 2.36, and 95% confidence intervals (CI): 1.20-4.63, as well as in Tasmanian cases only (OR = 2.33, 95% CI: 1.06-5.13), compared with controls. The results suggest that the FMR1 grey zone alleles, as well as premutation alleles, might contribute to the aetiology of disorders associated with parkinsonism.

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Figures

Fig 1
Fig 1
Kernel density estimate of the distributions of CGG repeats in the sample with parkinsonism, and in the control sample of Tasmanian newborns.
See this image and copyright information in PMC

References

    1. Hagerman RJ, Leehey M, Heinrichs W, et al. Intention tremor, Parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology. 2001;57:127–130. - PubMed
    1. Verkerk AJ, Pieretti M, Sutcliffe JS, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991;65:905–914. - PubMed
    1. Maddalena A, Richards CS, McGinniss MJ, et al. Technical standards and guidelines for fragile X: The first of series of disease specific supplements to the Standard Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics. Quality Assurance Subcommittee of the Laboratory Practice Committee. Genet Med. 2001;3:200–205. - PMC - PubMed
    1. Jacquemont S, Hagerman RJ, Leehey MD, et al. Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA. 2004;291(4):460–469. - PubMed
    1. Jacquemont S, Hagerman RJ, Leehey M, et al. Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. Am J Hum Genet. 2003;72:869–878. - PMC - PubMed

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