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

Hdl Handle:
http://hdl.handle.net/10147/207705
Title:
Dementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.
Authors:
Murphy, S; Gorman, G; Beetz, C; Byrne, P; Dytko, M; McMonagle, P; Kinsella, K; Farrell, M; Hutchinson, M
Affiliation:
Department of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. mhutchin@iol.ie
Citation:
Neurology. 2009 Aug 4;73(5):378-84.
Journal:
Neurology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207705
DOI:
10.1212/WNL.0b013e3181b04c6c
PubMed ID:
19652142
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
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
ISSN:
1526-632X (Electronic); 0028-3878 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMurphy, Sen_GB
dc.contributor.authorGorman, Gen_GB
dc.contributor.authorBeetz, Cen_GB
dc.contributor.authorByrne, Pen_GB
dc.contributor.authorDytko, Men_GB
dc.contributor.authorMcMonagle, Pen_GB
dc.contributor.authorKinsella, Ken_GB
dc.contributor.authorFarrell, Men_GB
dc.contributor.authorHutchinson, Men_GB
dc.date.accessioned2012-02-01T10:35:28Z-
dc.date.available2012-02-01T10:35:28Z-
dc.date.issued2012-02-01T10:35:28Z-
dc.identifier.citationNeurology. 2009 Aug 4;73(5):378-84.en_GB
dc.identifier.issn1526-632X (Electronic)en_GB
dc.identifier.issn0028-3878 (Linking)en_GB
dc.identifier.pmid19652142en_GB
dc.identifier.doi10.1212/WNL.0b013e3181b04c6cen_GB
dc.identifier.urihttp://hdl.handle.net/10147/207705-
dc.description.abstractBACKGROUND: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdenosine Triphosphatases/*geneticsen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAge of Onseten_GB
dc.subject.meshAgeden_GB
dc.subject.meshBrain/metabolism/pathology/physiopathologyen_GB
dc.subject.meshCognition Disorders/diagnosis/genetics/physiopathologyen_GB
dc.subject.meshDNA Mutational Analysisen_GB
dc.subject.meshDementia/*diagnosis/*genetics/physiopathologyen_GB
dc.subject.meshDisability Evaluationen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGene Deletionen_GB
dc.subject.meshGene Frequency/geneticsen_GB
dc.subject.meshGenetic Markers/geneticsen_GB
dc.subject.meshGenetic Predisposition to Disease/*geneticsen_GB
dc.subject.meshGenetic Testingen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInclusion Bodies/metabolism/pathologyen_GB
dc.subject.meshInheritance Patternsen_GB
dc.subject.meshLongitudinal Studiesen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMembrane Proteins/geneticsen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNeuropsychological Testsen_GB
dc.subject.meshPedigreeen_GB
dc.subject.meshSpastic Paraplegia, Hereditary/*complications/*geneticsen_GB
dc.subject.meshUbiquitin/analysis/metabolismen_GB
dc.titleDementia in SPG4 hereditary spastic paraplegia: clinical, genetic, and neuropathologic evidence.en_GB
dc.contributor.departmentDepartment of Neurology, St. Vincent's University Hospital, Elm Park, Dublin 4,, Ireland. mhutchin@iol.ieen_GB
dc.identifier.journalNeurologyen_GB
dc.description.provinceLeinster-

Related articles on PubMed

All Items in Lenus, The Irish Health Repository are protected by copyright, with all rights reserved, unless otherwise indicated.