Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients

Memory Clinic, Center for Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Lehener Str. 88, 79106 Freiburg, Germany.
Journal of Neurology (Impact Factor: 3.38). 08/2009; 256(12):2043-51. DOI: 10.1007/s00415-009-5248-6
Source: PubMed


Mutations of the progranulin gene lead to progranulin haploinsufficiency and to frontotemporal lobar degeneration (FTD) with TDP-43 positive inclusions. It is assumed that unknown genetic, epigenetic and environmental factors are responsible for the observed marked degree of phenotypic variability among mutation carriers. This is the first published series of German FTD cases screened for progranulin mutations. Mean age at onset was 62 years, 19 patients (24%) had a positive family history of dementia, and 11 patients (14%) had a positive family history for probable FTD. Data on FTD subtypes are presented. Two mutations were identified (3%), one of which has been described previously. Clinically, both patients showed the frontal-behavioural variant type of FTD. Remarkably, a sibling of one case presented with progressive nonfluent aphasia, clinically distinct from the brother. We also performed quantitative PCR analyses to detect potential whole progranulin gene and exon deletions. Here, results were negative.

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Available from: Klaus Schmidtke, Oct 15, 2014
    • "© 2013 – IOS Press and the authors. All rights reserved A U T H O R C O P Y 70 L. Benussi et al. / Estimating the Age of the Most Common Italian GRN Mutation GRN mutation frequency can be up to 26% [7] [8] [9] [10] [11] [12]. Even though all GRN loss-of-function mutations are expected to cause the disease through a common mechanism (haploinsufficiency), the spectrum of clinical presentations associated with mutations in GRN is highly heterogeneous. "
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    • "Most of the mutations lead to frameshift and premature stop codons. E.g., point mutations were identified in two cases of a German cohort of 79 patients (Schlachetzki, Schmidtke et al. 2009). Pathogenic mutations in PGRN invariably lead to mutant mRNA transcripts, which undergo nonsense-mediated decay, thereby resulting in haploinsufficiency (Baker, Mackenzie et al. 2006; Cruts, Gijselinck et al. 2006). "
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