title: Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients.
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.
authors.affiliation: Memory Clinic, Center for Geriatrics and Gerontology Freiburg, University Hospital Freiburg, Lehener Str. 88, 79106 Freiburg, Germany. johannes.schlachetzki@uk-erlangen.de
authors.forename: Johannes Carolus Magnus
authors.initials: JC
authors.lastname: Schlachetzki
authors.forename: Klaus
authors.initials: K
authors.lastname: Schmidtke
authors.forename: Jan
authors.initials: J
authors.lastname: Beckervordersandforth
authors.forename: Wiktor
authors.initials: W
authors.lastname: Borozdin
authors.forename: Christian
authors.initials: C
authors.lastname: Wilhelm
authors.forename: Michael
authors.initials: M
authors.lastname: Hüll
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kohlhase
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001923:Brain Chemistry / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005787:Gene Frequency / Q000502:physiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005858:Germany; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins