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Reduced telomere length in individuals with FMR1 premutations and full mutations

Authors

  • Edmund C. Jenkins,

    Corresponding author
    1. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York
    • Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314.

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  • Flora Tassone,

    1. M.I.N.D. Institute, University of California, Department of Pediatrics, Davis Health System, Sacramento, California
    2. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California
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  • Lingling Ye,

    1. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York
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  • André T. Hoogeveen,

    1. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
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  • W. Ted Brown,

    1. Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York
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  • Randi J. Hagerman,

    1. M.I.N.D. Institute, University of California, Department of Pediatrics, Davis Health System, Sacramento, California
    2. Department of Pediatrics, UC Davis Health System, Sacramento, California
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  • Paul J. Hagerman

    1. M.I.N.D. Institute, University of California, Department of Pediatrics, Davis Health System, Sacramento, California
    2. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, California
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  • How to Cite this Article: Jenkins EC, Tassone F, Ye L, Hoogeveen AT, Brown WT, Hagerman, RJ, Hagerman PJ. 2012. Reduced telomere length in individuals with FMR1 premutations and full mutations. Am J Med Genet Part A. 158A:1060–1065.

Abstract

We reported previously that 10 older men (66.4 ± 4.6 years) with premutation alleles (55–200 CGG repeats) of the FMR1 gene, with or without FXTAS, had decreased telomere length when compared to sex- and age-matched controls. Extending our use of light intensity measurements from a telomere probe hybridized to interphase preparations, we have now found shortened telomeres in 9 younger male premutation carriers (31.7 ± 17.6 years). We have also shown decreased telomere length in T lymphocytes from 6 male individuals (12.0 ± 1.8 years) with full mutation FMR1 alleles (>200 CGG repeats). These findings support our hypothesis that reduced telomere length is a component of the sub-cellular pathology of FMR1-associated disorders. The experimental approach involved pair-wise comparisons of light intensity values of 20 cells from an individual with either premutation or full mutation CGG-repeat expansions relative to an equivalent number of cells from a sex- and age-matched control. In addition, we demonstrated reduced telomere size in T-lymphocyte cultures from eight individuals with the FMR1 premutation using six different measures. Four relied on detection of light intensity differences, and two involved measuring the whole chromosome, including the telomere, in microns. This new approach confirmed our findings with light intensity measurements and demonstrated the feasibility of direct linear measurements for detecting reductions in telomere size. We have thus confirmed our hypothesis that reduced telomere length is associated with both premutation and full mutation-FMR1 alleles and have demonstrated that direct measurements of telomere length can reliably detect such reductions. © 2012 Wiley Periodicals, Inc.

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