Article

Late-onset frontotemporal dementia associated with a novel PGRN mutation

Alzheimer's Disease and Cognitive Disorders Unit, Neurology Service, Hospital Clínic and Institut d'Investigació Biomèdica August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Journal of Neural Transmission (Impact Factor: 2.87). 02/2007; 114(8):1051-4. DOI: 10.1007/s00702-007-0716-6
Source: PubMed

ABSTRACT We describe a new mutation in the PGRN gene (A303AfsX57) associated with late-onset frontotemporal dementia and with "cat's eye" shaped intranuclear and cytoplasmatic ubiquitin immunoreactive inclusions in the neuropathological exam. The A303AfsX57 mutation is consistent with a nucleotide deletion in exon 8 (c908delC). This deletion causes a frameshift at codon 303 that introduces a premature termination codon (A303AfsX57).

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    • "The loss of functional protein is mainly the result of loss of GRN transcript caused by NMD of transcripts containing PTCs (n 5 52) or by nuclear degradation of transcripts retaining the first intron due to splice-site mutations in intron 1 (n 5 2) [Cruts et al., 2006; Le Ber et al., 2007]. PTCs can be the result from nonsense mutations (n 5 12), splice-site mutations (n 5 10), and small insertions/deletions (n 5 30) [Cruts et al., 2006; Baker et al., 2006; Huey et al., 2006; Pickering-Brown et al., 2006, 2008; Boeve et al., 2006; Masellis et al., 2006; Gass et al., 2006; Benussi et al., 2008; Bronner et al., 2007; Mesulam et al., 2007; Behrens et al., 2007; Leverenz et al., 2007; Bruni et al., 2007; Van Deerlin et al., 2007; Brouwers et al., 2007; Rademakers et al., 2007; Llado et al., 2007; Le Ber et al., 2007; Davion et al., 2007; Kelley et al., in press; Spina et al., 2007a; Mukherjee et al., 2008; Beck et al., 2008; Le Ber et al., 2008]. Second, loss of translation as a result of mutations affecting the Kozak sequence (n 5 4) [Cruts et al., 2006; Baker et al., 2006; Pickering-Brown et al., 2006; Boeve et al., 2006; Gass et al., 2006; Le Ber et al., 2008] and reduction of secreted protein due to missense mutations affecting the signal sequence (n 5 2) [Mukherjee et al., 2006; Gass et al., 2006; Kelley et al., in press; Mukherjee et al., 2008; Le Ber et al., 2008], results in reduced GRN. "
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