title: Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Lee
authors.forename: Ricardo E
authors.initials: RE
authors.lastname: Madrid
authors.forename: Karen
authors.initials: K
authors.lastname: Sperle
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Ritterson
authors.forename: Grace M
authors.initials: GM
authors.lastname: Hobson
authors.forename: James
authors.initials: J
authors.lastname: Garbern
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Ken
authors.initials: K
authors.lastname: Inoue
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D006801:Humans; D062792:MARVEL Domain-Containing Proteins; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009154:Mutation; D009431:Neural Conduction / Q000502:physiology; D009693:Nucleic Acid Hybridization / Q000379:methods; D020371:Pelizaeus-Merzbacher Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D011510:Proteolipids; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
chemical_list: D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins; C094765:PLP2 protein, human; D011510:Proteolipids