Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect.
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.
Lee
Jennifer A
JA
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
Madrid
Ricardo E
RE
Sperle
Karen
K
Ritterson
Carolyn M
CM
Hobson
Grace M
GM
Garbern
James
J
Lupski
James R
JR
Inoue
Ken
K
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
D062792:MARVEL Domain-Containing Proteins; D008565:Membrane Proteins; C094765:PLP2 protein, human; D011510:Proteolipids