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

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Abstract

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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Authors and Affiliations

  1. Memory Clinic, Center for Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Lehener Str. 88, 79106, Freiburg, Germany

    Johannes Carolus Magnus Schlachetzki, Klaus Schmidtke & Michael Hüll

  2. Department of Psychiatry and Psychotherapy, University Hospital Freiburg, Hauptstr, 5, 79104, Freiburg, Germany

    Johannes Carolus Magnus Schlachetzki

  3. Center For Human Genetics, Heinrich-von-Stephan-Str. 5, 79100, Freiburg, Germany

    Jan Beckervordersandforth, Wiktor Borozdin, Christian Wilhelm & Jürgen Kohlhase

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  1. Johannes Carolus Magnus Schlachetzki
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  2. Klaus Schmidtke
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  3. Jan Beckervordersandforth
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Correspondence to Johannes Carolus Magnus Schlachetzki.

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J. C. M. Schlachetzki and K. Schmidtke contributed equally to this work.

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Schlachetzki, J.C.M., Schmidtke, K., Beckervordersandforth, J. et al. Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients. J Neurol 256, 2043–2051 (2009). https://doi.org/10.1007/s00415-009-5248-6

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