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Exome sequencing: an efficient diagnostic tool for complex neurodegenerative disorders

Authors

  • M. B. Hammer,

    1. Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia
    2. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
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  • G. Eleuch-Fayache,

    1. Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia
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  • J. R. Gibbs,

    1. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    2. Reta Lilla Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK
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  • S. K. Arepalli,

    1. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
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  • S. B. Chong,

    1. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
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  • C. Sassi,

    1. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    2. Reta Lilla Weston Laboratories and Departments of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, UK
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  • Y. Bouhlal,

    1. Institute of Human Genetics, UCSF, San Francisco, CA, USA
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  • F. Hentati,

    1. Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia
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  • R. Amouri,

    1. Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia
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  • A. B. Singleton

    Corresponding author
    1. Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
    • Department of Molecular Neurobiology and Neuropathology, National Institute of Neurology, La Rabta, Tunis, Tunisia
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Correspondence: Andrew B. Singleton, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Room 1A1014, Bethesda, MD 20892, USA (tel.: 001 301 451 6079; fax: 001 301 451 5466; e-mail: singleta@mail.nih.gov).

Abstract

Background and purpose

Autosomal recessive cerebellar ataxia (ARCA) comprises a large and heterogeneous group of neurodegenerative disorders. We studied three families diagnosed with ARCA.

Methods

To determine the gene lesions responsible for their disorders, we performed high-density single-nucleotide polymorphism genotyping and exome sequencing.

Results

We identified a new mutation in the SACS gene and a known mutation in SPG11. Notably, we also identified a homozygous variant in APOB, a gene previously associated with ataxia.

Conclusions

These findings demonstrate that exome sequencing is an efficient and direct diagnostic tool for identifying the causes of complex and genetically heterogeneous neurodegenerative diseases, early-stage disease or cases with limited clinical data.

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