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Autosomal recessive hereditary spastic paraplegia—clinical and genetic characteristics of a well-defined cohort

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Abstract

We describe the clinical and genetic features of a well-characterized cohort of patients with autosomal recessive hereditary spastic paraplegia (ARHSP) in the province of Ontario. Patients with documented corticospinal tract abnormalities were screened by whole gene sequencing and multiplex ligation probe amplification for mutations in nine genes known to cause ARHSP. Of a cohort of 39 patients, a genetic diagnosis was established in 17 (44 %) and heterozygous mutations were detected in 8 (21 %). Mutations were most frequent in SPG7 (12 patients), followed by SPG11 (10 patients), PNPLA6 (SPG39, 2 patients), and ZFYVE26 (SPG15, 2 patients). Although there are associations between some clinical manifestations of ARHSP and specific genes, many patients are tested at an early stage of the disease when phenotype/genotype correlations are not obvious. Accurate molecular characterization of well-phenotyped cohorts of patients will be essential to establishing the natural history of these rare degenerative disorders to enable future clinical trials.

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Acknowledgments

The authors would like to thank the patients and their families for participating in the study. We also thank Paige Rebeiro for expert technical assistance. This study was funded by the National Institutes of Health Office of Rare Diseases Research Collaboration Education and Test Translation Program.

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Authors and Affiliations

  1. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Canada

    G. Yoon

  2. Division of Neurology, The Hospital for Sick Children, Toronto, Canada

    G. Yoon & B. Banwell

  3. Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada

    B. Baskin & P. N. Ray

  4. Division of Neuromuscular and Neurometabolic Disorders, McMaster University, Hamilton, Canada

    M. Tarnopolsky

  5. Department of Genetics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    K. M. Boycott

  6. Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    M. T. Geraghty & E. Sell

  7. Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre, London, Canada

    S. Goobie

  8. Genetics Program, North York General Hospital, Toronto, Canada

    W. Meschino

  9. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden

    B. Baskin

  10. Department of Molecular Genetics, The University of Toronto, Toronto, Canada

    P. N. Ray

  11. Divisions of Neurology and Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    G. Yoon

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  1. G. Yoon
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  2. B. Baskin
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  5. M. T. Geraghty
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  6. E. Sell
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  7. S. Goobie
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  8. W. Meschino
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  9. B. Banwell
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  10. P. N. Ray
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Correspondence to G. Yoon.

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Yoon, G., Baskin, B., Tarnopolsky, M. et al. Autosomal recessive hereditary spastic paraplegia—clinical and genetic characteristics of a well-defined cohort. Neurogenetics 14, 181–188 (2013). https://doi.org/10.1007/s10048-013-0366-9

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  • DOI: https://doi.org/10.1007/s10048-013-0366-9

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