Neurobiology of Disease (Feb 2003)
TorsinA protein and neuropathology in early onset generalized dystonia with GAG deletion
- Kevin Rostasy,
- Sarah J Augood,
- Jeffrey W Hewett,
- Joanne Chung-on Leung,
- Hikaru Sasaki,
- Laurie J Ozelius,
- Vijaya Ramesh,
- David G Standaert,
- Xandra O Breakefield,
- John C Hedreen
Affiliations
- Kevin Rostasy
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Sarah J Augood
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Jeffrey W Hewett
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Joanne Chung-on Leung
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Hikaru Sasaki
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Laurie J Ozelius
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Vijaya Ramesh
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- David G Standaert
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Xandra O Breakefield
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- John C Hedreen
- Pediatric Neurology Floating Hospital, Boston, MA, USA; Department of Pediatric Neurology, Georg-August University of Göttingen, Germany; Neurodegenerative Center, Massachusetts General Hospital, Charlestown, MA, USA; Molecular Neurogenetics Unit, Massachusetts General Hospital, Charlestown, MA, USA; Departments of Neurology and Neuroscience Program, Harvard Medical School, Boston, MA, USA; Molecular Neuro-Oncology Laboratory, Neurosurgery Service, Massachusetts General Hospital, Charlestown, MA, USA; Department of Molecular Genetics, Albert Einstein College Med., Bronx, NY 10461, USA; Department of Psychiatry, No. 1007, Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA; Department of Psychiatry, Harvard University, McLean Hospital, Belmont, MA, USA
- Journal volume & issue
-
Vol. 12,
no. 1
pp. 11 – 24
Abstract
Familial, early onset, generalized torsion dystonia is the most common and severe primary dystonia. Most cases are caused by a 3-bp deletion (GAG) in the coding region of the TOR1A (DYT1) gene, which is widely expressed in human brain and encodes the protein torsinA. This study compares neuropathology and torsinA expression in the normal human brain with that in dystonia cases with and without the GAG deletion. TorsinA-like protein was expressed in neuronal cytoplasm throughout the human brain, including cerebellum, substantia nigra, hippocampus, and neostriatum, with higher levels in specific neurons. This immunostaining pattern was not discernibly different in dystonia and normal brains in midbrain and neostriatal regions. However, nigral dopaminergic neurons appeared to be larger in both GAG-deletion and non-GAG-deletion dystonia brains compared to normal, and may be more closely spaced in GAG-deletion brains. Beyond these apparent changes in neuronal size and spacing in dystonia brains, there was no indication of neuron loss, inflammation, DNA strand breaks, or altered distribution of torsin-like immunoreactivity, supporting a functional rather than degenerative etiology of early onset torsion dystonia.
