Acta Neuropathologica

, Volume 124, Issue 2, pp 285–291

TDP-43 pathology in a case of hereditary spastic paraplegia with a NIPA1/SPG6 mutation

  • Maria Martinez-Lage
  • Laura Molina-Porcel
  • Dana Falcone
  • Leo McCluskey
  • Virginia M.-Y. Lee
  • Vivianna M. Van Deerlin
  • John Q. Trojanowski
Case Reports

DOI: 10.1007/s00401-012-0947-y

Cite this article as:
Martinez-Lage, M., Molina-Porcel, L., Falcone, D. et al. Acta Neuropathol (2012) 124: 285. doi:10.1007/s00401-012-0947-y

Abstract

Mutations in NIPA1 (non-imprinted in Prader–Willi/Angelman syndrome) have been described as a cause of autosomal dominant hereditary spastic paraplegia (HSP) known as SPG6 (spastic paraplegia-6). We present the first neuropathological description of a patient with a NIPA1 mutation, and clinical phenotype of complicated HSP with motor neuron disease-like syndrome and cognitive decline. Postmortem examination revealed degeneration of lateral corticospinal tracts and dorsal columns with motor neuron loss. TDP-43 immunostaining showed widespread spinal cord and cerebral skein-like and round neuronal cytoplasmic inclusions. We ruled out NIPA1 mutations in 419 additional cases of motor neuron disease. These findings suggest that hereditary spastic paraplegia due to NIPA1 mutations could represent a TDP-43 proteinopathy.

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Maria Martinez-Lage
    • 2
  • Laura Molina-Porcel
    • 2
  • Dana Falcone
    • 2
  • Leo McCluskey
    • 3
  • Virginia M.-Y. Lee
    • 2
  • Vivianna M. Van Deerlin
    • 1
  • John Q. Trojanowski
    • 2
  1. 1.Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research (CNDR)University of Pennsylvania Health SystemPhiladelphiaUSA
  2. 2.Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research (CNDR)University of Pennsylvania Health SystemPhiladelphiaUSA
  3. 3.Department of NeurologyUniversity of Pennsylvania Health SystemPhiladelphiaUSA