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Published in: Acta Neuropathologica 2/2012

01-08-2012 | Case Reports

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

Authors: Maria Martinez-Lage, Laura Molina-Porcel, Dana Falcone, Leo McCluskey, Virginia M.-Y. Lee, Vivianna M. Van Deerlin, John Q. Trojanowski

Published in: Acta Neuropathologica | Issue 2/2012

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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.
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Metadata
Title
TDP-43 pathology in a case of hereditary spastic paraplegia with a NIPA1/SPG6 mutation
Authors
Maria Martinez-Lage
Laura Molina-Porcel
Dana Falcone
Leo McCluskey
Virginia M.-Y. Lee
Vivianna M. Van Deerlin
John Q. Trojanowski
Publication date
01-08-2012
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 2/2012
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-012-0947-y

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