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FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile

Authors

  • L. Santa María,

    Corresponding author
    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
    • Corresponding author: Lorena Santa María, Molecular Cytogenetics Laboratory, INTA University of Chile, El Líbano 5524, Santiago, Chile.

      Tel.: +56 2 29781494;

      fax: +56 2 29781489;

      e-mail: lsantamaria@inta.uchile.cl

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    • These authors share the responsibility of the first author.
  • A. Pugin,

    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
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    • These authors share the responsibility of the first author.
  • M.A. Alliende,

    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
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  • S. Aliaga,

    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
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  • B. Curotto,

    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
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  • T. Aravena,

    1. Center for Diagnosis and Treatment of Fragile X Syndrome (CDTSXF), INTA University of Chile, Santiago, Chile
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  • H.-T. Tang,

    1. Department of Biochemistry and Molecular Medicine, University of California Davis, CA, USA
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  • G. Mendoza-Morales,

    1. Department of Biochemistry and Molecular Medicine, University of California Davis, CA, USA
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  • R. Hagerman,

    1. MIND Institute, University of California, Davis Medical Center, Sacramento, CA, USA
    2. Department of Pediatrics, University of California, Davis Medical Center, Sacramento, CA, USA
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  • F. Tassone

    1. Department of Biochemistry and Molecular Medicine, University of California Davis, CA, USA
    2. MIND Institute, University of California, Davis Medical Center, Sacramento, CA, USA
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  • R. H. has received funding from Novartis, Roche, Seaside Therapeutics, Curemark and Forest for clinical trials in fragile X syndrome or autism. She has also consulted with Novartis regarding targeted treatments for fragile X syndrome. A.P. has received funding from Roche for clinical trials in fragile X syndrome. The other authors declare no conflicts of interest.

Abstract

Carriers of an FMR1 premutation allele (55–200 CGG repeats) often develop the neurodegenerative disorders, fragile X-associated tremor/ataxia syndrome (FXTAS). Neurological signs of FXTAS, parkinsonism and rapid onset of cognitive decline have not been reported in individuals with an unmethylated full mutation (FM). Here, we report a Chilean family affected with FXS, inherited from a parent carrier of an FMR1 unmethylated full mosaic allele, who presented with a fast progressing FXTAS. This case suggests that the definition of FXTAS may need to be broadened to not only include those with a premutation but also those with an expanded allele in FM range with a lack of methylation leading to elevated FMR1-mRNA expression levels and subsequent RNA toxicity.

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