Neuroserpin mutation S52R causes Neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy

Masaki Takao, Merrill Benson, Jill R. Murrell, Masahide Yazaki, Pedro Piccardo, Frederick Unverzagt, Richard L. Davis, Peter D. Holohan, Daniel A. Lawrence, Rosemarie Richardson, Martin Farlow, Bernardino Ghetti

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Mutations in the Neuroserpin gene have been reported to cause familial presenile dementia. We describe a new family in which the S52R Neuroserpin mutation is associated with progressive myoclonus epilepsy in 2 siblings. The proband presented myoclonus and epilepsy at age 24, his brother and mother presented a similar disorder when they were 25. A clinical diagnosis of progressive myoclonus epilepsy was made on the proband and his brother. Skin and liver biopsies did not reveal the presence of cytological alterations in the proband. His neurological status worsened over the subsequent 19 yr during which he became demented and had uncontrollable seizures. He died at 43 yr of age from aspiration pneumonia. Neuropathologically, eosinophilic bodies, which were positive for periodic acid-Schiff and immunoreactive with antibodies against human neuroserpin, were present in the perikarya and cell processes of the neurons. They were found in large numbers in the cerebral cortex and substantia nigra and to a lesser extent, in most subcortical gray areas, spinal cord, and dorsal root ganglia. By electron microscopy, the intracytoplasmic bodies were contained within the membranes of the rough endoplasmic reticulum. Occasionally neuroserpin immunopositivity was seen throughout the cytoplasm, even without the presence of well-defined bodies. Our study characterizes for the first time the neuropathologic phenotype associated with hereditary progressive myoclonus epilepsy caused by the S52R Neuroserpin mutation.

Original languageEnglish
Pages (from-to)1070-1086
Number of pages17
JournalJournal of Neuropathology and Experimental Neurology
Volume59
Issue number12
StatePublished - 2000

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Progressive Myoclonic Epilepsy
Neurons
Mutation
Myoclonic Epilepsy
Aspiration Pneumonia
Periodic Acid
Rough Endoplasmic Reticulum
Spinal Nerve Roots
Spinal Ganglia
Substantia Nigra
Cerebral Cortex
Dementia
Spinal Cord
Electron Microscopy
Alzheimer Disease
Cytoplasm
Seizures
neuroserpin
Phenotype
Biopsy

Keywords

  • Dementia
  • Lafora disease
  • Mutation
  • Neuroserpin
  • Progressive myoclonus epilepsy
  • Seizures

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Neuroserpin mutation S52R causes Neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy. / Takao, Masaki; Benson, Merrill; Murrell, Jill R.; Yazaki, Masahide; Piccardo, Pedro; Unverzagt, Frederick; Davis, Richard L.; Holohan, Peter D.; Lawrence, Daniel A.; Richardson, Rosemarie; Farlow, Martin; Ghetti, Bernardino.

In: Journal of Neuropathology and Experimental Neurology, Vol. 59, No. 12, 2000, p. 1070-1086.

Research output: Contribution to journalArticle

Takao, Masaki ; Benson, Merrill ; Murrell, Jill R. ; Yazaki, Masahide ; Piccardo, Pedro ; Unverzagt, Frederick ; Davis, Richard L. ; Holohan, Peter D. ; Lawrence, Daniel A. ; Richardson, Rosemarie ; Farlow, Martin ; Ghetti, Bernardino. / Neuroserpin mutation S52R causes Neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy. In: Journal of Neuropathology and Experimental Neurology. 2000 ; Vol. 59, No. 12. pp. 1070-1086.
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AU - Unverzagt, Frederick

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