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Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect

Authors

  • Jennifer A. Lee BS,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
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  • Ricardo E. Madrid MD,

    1. New York State Institute for Basic Research in Developmental Disabilities, George A. Jervis Clinic, Staten Island, NY
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  • Karen Sperle MS,

    1. Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Nemours Children's Clinic, Wilmington, DE
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  • Carolyn M. Ritterson BS,

    1. Department of Biology, Boston University, Boston, MA
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  • Grace M. Hobson PhD,

    1. Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Nemours Children's Clinic, Wilmington, DE
    2. Department of Pediatrics, Jefferson Medical College, Philadelphia, PA
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  • James Garbern MD, PhD,

    1. Department of Neurology and Center of Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI
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  • James R. Lupski MD, PhD,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
    2. Department of Pediatrics, Baylor College of Medicine, Houston, TX
    3. Texas Children's Hospital, Houston, TX
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  • Ken Inoue MD, PhD

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
    2. Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    • Department of Mental Retardation and Birth Defect Research National, Institute of Neurology National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502
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Abstract

Objective

To report an association between spastic paraplegia type 2 with axonal peripheral neuropathy and apparent proteolipid protein gene (PLP1) silencing in a family.

Methods

Pulsed-field gel electrophoresis, custom array comparative genomic hybridization, and semi-quantitative multiplex polymerase chain reaction analyses were used to examine the PLP1 genomic region.

Results

Electrodiagnostic studies and a sural nerve biopsy showed features of a dystrophic axonal neuropathy. Molecular studies identified a small duplication downstream of PLP1.

Interpretation

We propose the duplication to result in PLP1 gene silencing by virtue of a position effect. Our observations suggest that genomic rearrangements that do not include PLP1 coding sequences should be considered as yet another potential mutational mechanism underlying PLP1-related dysmyelinating disorders. Ann Neurol 2005

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