Journal article
The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene
Acta neuropathologica, Vol.122(1), pp.99-110
07/01/2011
DOI: 10.1007/s00401-011-0816-0
PMID: 21424531
Abstract
Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and genetically heterogeneous. Recent descriptions of a pathological sub-type that is ubiquitin positive, TDP-43 negative and immunostains positive for the Fused in Sarcoma protein (FUS) raises the question whether it is associated with a distinct clinical phenotype identifiable on clinical grounds, and whether mutations in the Fused in Sarcoma gene (FUS) might also be associated with FTLD. Examination of a pathological series of 118 cases of FTLD from two centres, showing tau-negative, ubiquitin-positive pathology, revealed FUS pathology in five patients, four classified as atypical FTLD with ubiquitin inclusions (aFTLD-U), and one as neuronal intermediate filament inclusion disease (NIFID). The aFTLD-Ucases had youthful onset (22-46 years), an absence of strong family history, a behavioural syndrome consistent with frontotemporal dementia (FTD) and severe caudate atrophy. Their cognitive/behavioural profile was distinct, characterised by prominent obsessionality, repetitive behaviours and rituals, social withdrawal and lack of engagement, hyperorality with pica, and marked stimulus-bound behaviour including utilisation behaviour. They conformed to the rare behavioural sub-type of FTD identified previously by us as the "stereotypic'' form, and linked to striatal pathology. Cognitive evaluation revealed executive deficits in keeping with subcortical-frontal dysfunction, but no cortical deficits in language, perceptuospatial skills or praxis. The patient with NIFID was older and exhibited aphasia and dyspraxia. No patient had clinical evidence of motor neurone disease during life, or a mutation in the FUS gene. In the complementary clinical study of 312 patients with clinical syndromes of FTLD, genetic analysis revealed a 6 bp deletion in FUS in 3 patients, of questionable significance. One presented a prototypical picture of FTD, another expressive language disorder, and the third semantic dementia. None showed the early onset age or distinctive 'stereotypic' picture of patients with aFTLD-U. We conclude that aFTLD-U is associated with a distinct clinical form of frontotemporal dementia, potentially allowing identification of such patients in life with a high degree of precision. Whether mutations in the FUS gene cause some cases of FTLD remains unresolved.
Details
- Title: Subtitle
- The most common type of FTLD-FUS (aFTLD-U) is associated with a distinct clinical form of frontotemporal dementia but is not related to mutations in the FUS gene
- Creators
- Julie S. Snowden - University of ManchesterQuan Hu - University of ManchesterSara Rollinson - University of ManchesterNicola Halliwell - University of ManchesterAndrew Robinson - University of ManchesterYvonne S. Davidson - University of ManchesterParastoo Momeni - Texas Tech University Health Sciences CenterAtik Baborie - Walton CentreTimothy D. Griffiths - North Tyneside General HospitalEvelyn Jaros - Royal Victoria InfirmaryRobert H. Perry - Royal Victoria InfirmaryAnna Richardson - Salford Royal NHS Foundation TrustStuart M. Pickering-Brown - University of ManchesterDavid Neary - Salford Royal NHS Foundation TrustDavid M. A. Mann - Salford Royal Fdn NHS Trust, Cerebral Funct Unit, Mental Hlth & Neurodegenerat Res Grp, Greater Manchester Neurosci Ctr, Salford M6 8HD, Lancs, England
- Resource Type
- Journal article
- Publication Details
- Acta neuropathologica, Vol.122(1), pp.99-110
- Publisher
- Springer Nature
- DOI
- 10.1007/s00401-011-0816-0
- PMID
- 21424531
- ISSN
- 0001-6322
- eISSN
- 1432-0533
- Number of pages
- 12
- Grant note
- MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) Wellcome Trust G0502157; G0400074; G1100540; G0701441; G0900652 / Medical Research Council; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) UK NIHR Biomedical Research Centre for Ageing and Age-related disease; National Institutes of Health Research (NIHR) Alzheimer's Research Trust Alzheimer's Society through Manchester Brain Bank under the Brains for Dementia Research (BDR) initiative G1100540; G0400074; G0502157; G0900652; G0701441 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) 111 Project; Ministry of Education, China - 111 Project
- Language
- English
- Date published
- 07/01/2011
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984627294402771
Metrics
9 Record Views