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.
Publication types
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Case Reports
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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DNA Mutational Analysis / methods
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Electrophoresis, Polyacrylamide Gel / methods
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Humans
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MARVEL Domain-Containing Proteins
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Magnetic Resonance Imaging / methods
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Male
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Membrane Proteins / genetics*
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Microscopy, Electron, Transmission / methods
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Mutation*
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Neural Conduction / physiology
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Nucleic Acid Hybridization / methods
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Pelizaeus-Merzbacher Disease / complications
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Pelizaeus-Merzbacher Disease / genetics*
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Pelizaeus-Merzbacher Disease / pathology
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Peripheral Nervous System Diseases / complications
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Peripheral Nervous System Diseases / genetics*
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Peripheral Nervous System Diseases / pathology
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Proteolipids
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Sural Nerve / metabolism
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Sural Nerve / pathology
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Sural Nerve / ultrastructure
Substances
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MARVEL Domain-Containing Proteins
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Membrane Proteins
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PLP2 protein, human
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Proteolipids