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Spastic paraplegia type 2 associated with axonal neuropathy and apparent PLP1 position effect
Author(s) -
Lee Jennifer A.,
Madrid Ricardo E.,
Sperle Karen,
Ritterson Carolyn M.,
Hobson Grace M.,
Garbern James,
Lupski James R.,
Inoue Ken
Publication year - 2006
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20732
Subject(s) - gene duplication , proteolipid protein 1 , paraplegia , spastic , genetics , biology , medicine , neuroscience , gene , myelin , physical medicine and rehabilitation , spinal cord , central nervous system , myelin basic protein , cerebral palsy
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