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 semiquantitative 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.