Publication

Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.

Murphy, S
; 
Gorman, G
; 
Beetz, C
; 
Byrne, P
; 
Dytko, M
; 
McMonagle, P
; 
Kinsella, K
; 
Farrell, M
; 
Hutchinson, M
Author
Murphy, S
 Gorman, G
 Beetz, C
 Byrne, P
 Dytko, M
 McMonagle, P
 Kinsella, K
 Farrell, M
 Hutchinson, M
Advisors
Editors
Other Contributors
Departments
Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. mhutchin@iol.ie
Date
2012-02-01T10:35:28Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Adenosine Triphosphatases/*genetics
Adult
Age of Onset
Aged
Brain/metabolism/pathology/physiopathology
Cognition Disorders/diagnosis/genetics/physiopathology
DNA Mutational Analysis
Dementia/*diagnosis/*genetics/physiopathology
Disability Evaluation
Female
Gene Deletion
Gene Frequency/genetics
Genetic Markers/genetics
Genetic Predisposition to Disease/*genetics
Genetic Testing
Genotype
Humans
Inclusion Bodies/metabolism/pathology
Inheritance Patterns
Longitudinal Studies
Male
Membrane Proteins/genetics
Middle Aged
Neuropsychological Tests
Pedigree
Spastic Paraplegia, Hereditary/*complications/*genetics
Ubiquitin/analysis/metabolism
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
URI
https://hdl.handle.net/10147/207705
Abstract
BACKGROUND: Cognitive impairment and dementia has been reported in autosomal dominant hereditary spastic paraparesis (HSP) linked to the SPG4 locus. There has only been one postmortem examination described; not all accept that progressive cognitive decline is a feature of this disorder. OBJECTIVE: A family with SPG4-HSP known to have a deletion of exon 17 in the spastin gene (SPG4delEx17) was cognitively assessed over a 7-year period. The index family member died and a postmortem examination was performed. METHODS: Thirteen family members older than 40 years were clinically and cognitively assessed using the Cambridge Cognitive Assessment over a 7-year period. The presence of SPG4delEx17 was assessed; a neuropathologic examination of the brain of the index family member was performed. RESULTS: Cognitive decline occurred in 6 of the 13 family members and in all 4 older than 60 years. Two genetic deletions were identified: SPG4delEx17 in 12 of the 13 family members and a deletion of SPG6 (SPG6del) in 5. Eight individuals had the SPG4delEx17 deletion only; 4 had evidence of progressive cognitive impairment. Four family members had both SPG4delEx17 and SPG6del; 2 of these had cognitive impairment. One family member with the SPG6del alone had neither HSP nor cognitive impairment. The index case with both deletions died with dementia; the brain showed widespread ubiquitin positivity within the neocortex and white matter. CONCLUSION: Cognitive decline and dementia is a feature of SPG4-HSP due to a deletion of exon 17 of the spastin gene.
Language
eng
Citation
Neurology. 2009 Aug 4;73(5):378-84.
ISSN
1526-632X (Electronic)
0028-3878 (Linking)
eISSN
ISBN
DOI
10.1212/WNL.0b013e3181b04c6c
PMID
19652142
PMCID
Sponsorships
Funding Sources
Funding Amounts
Grant Identifiers
Methodology
Duration
Ethical Approval