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Title
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Distinct clinical characteristics of **C9orf72** expansion carriers compared with **GRN, MAPT**, and nonmutation carriers in a Flanders-Belgian FTLD cohort
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Author
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Abstract
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| Objective To characterize patients with frontotemporal lobar degeneration (FTLD) with a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences in the clinical presentation compared with FTLD carriers of a mutation in GRN or MAPT or with patients with FTLD without mutation. Design Patient series. Setting Dementia clinics in Flanders, Belgium. Patients Two hundred seventy-five genetically and phenotypically thoroughly characterized patients with FTLD. Main Outcome Measures Clinical and demographic characteristics of 26 C9orf72 expansion carriers compared with patients with a GRN or MAPT mutation, as well as patients with familial and sporadic FTLD without mutation. Results C9orf72 expansion carriers developed FTLD at an early age (average, 55.3 years; range, 42-69 years), significantly earlier than in GRN mutation carriers or patients with FTLD without mutation. Mean survival (6.2 years; range, 1.5-17.0 years) was similar to other patient groups. Most developed behavioral variant frontotemporal dementia (85%), with disinhibited behavior as the prominent feature. Concomitant amyotrophic lateral sclerosis is a strong distinguishing feature for C9orf72 -associated FTLD. However, in most patients (73%), amyotrophic lateral sclerosis symptoms were absent. Compared with C9orf72 expansion carriers, nonfluent aphasia and limb apraxia were significantly more common in GRN mutation carriers. Conclusions C9orf72 -associated FTLD most often presents with early-onset behavioral variant frontotemporal dementia with disinhibition as the prominent feature, with or without amyotrophic lateral sclerosis. Based on the observed genotype-phenotype correlations between the different FTLD syndromes and different genetic causes, we propose a decision tree to guide clinical genetic testing in patients clinically diagnosed as having FTLD. |
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Language
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English
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Source (journal)
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JAMA neurology / American Medical Association. - Chicago, Ill., 2013, currens
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Publication
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Chicago, Ill.
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2013
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ISSN
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2168-6149
[print]
2168-6157
[online]
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Volume/pages
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70
:3
(2013)
, p. 365-373
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ISI
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000316804400011
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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