Neuropathological features of genetically confirmed DYT1 dystonia: investigating disease-specific inclusions.
BACKGROUND
Early onset isolated dystonia (DYT1) is linked to a three base pair deletion (ΔGAG) mutation in the TOR1A gene. Clinical manifestation includes intermittent muscle contraction leading to twisting movements or abnormal postures. Neuropathological studies on DYT1 cases are limited, most showing no significant abnormalities. In one study, brainstem intraneuronal inclusions immunoreactive for ubiquitin, torsinA and lamin A/C were described. Using the largest series reported to date comprising 7 DYT1 cases, we aimed to identify consistent neuropathological features in the disease and determine whether we would find the same intraneuronal inclusions as previously reported.


RESULTS
The pathological changes of brainstem inclusions reported in DYT1 dystonia were not replicated in our case series. Other anatomical regions implicated in dystonia showed no disease-specific pathological intracellular inclusions or evidence of more than mild neuronal loss.


CONCLUSIONS
Our findings suggest that the intracellular inclusions described previously in DYT1 dystonia may not be a hallmark feature of the disorder. In isolated dystonia, DYT1 in particular, biochemical changes may be more relevant than the morphological changes.
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. r.paudel@ucl.ac.uk.
Reema
R
Paudel
Queen Square Brain Bank, UCL Institute of Neurology, London, UK. a.kiely@ucl.ac.uk.
Aoife
A
Kiely
Queen Square Brain Bank, UCL Institute of Neurology, London, UK. abi.li@ucl.ac.uk.
Abi
A
Li
Queen Square Brain Bank, UCL Institute of Neurology, London, UK. t.lashley@ucl.ac.uk.
Tammaryn
T
Lashley
Queen Square Brain Bank, UCL Institute of Neurology, London, UK. r.bandopadhyay@ucl.ac.uk.
Rina
R
Bandopadhyay
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. j.hardy@ucl.ac.uk.
John
J
Hardy
Department of Neurology, Human Genetics, and Paediatrics, Emory University, Atlanta, Georgia, 30322, USA. hjinnah@emory.edu.
Hyder A
HA
Jinnah
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. k.bhatia@ucl.ac.uk.
Kailash
K
Bhatia
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. h.houlden@ucl.ac.uk.
Henry
H
Houlden
Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK. janice.holton@ucl.ac.uk.|Queen Square Brain Bank, UCL Institute of Neurology, London, UK. janice.holton@ucl.ac.uk.
Janice L
JL
Holton
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D020821:Dystonic Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D009474:Neurons / Q000378:metabolism / Q000473:pathology
D018832:Molecular Chaperones; C108175:TOR1A protein, human