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Novel Progranulin Mutation Detected in 2 Patients With FTLD
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. (Molekylär geriatrik)
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2011 (English)In: Alzheimer Disease and Associated Disorders, ISSN 0893-0341, E-ISSN 1546-4156, Vol. 25, no 2, 173-178 p.Article in journal (Refereed) Published
Abstract [en]

Frontotemporal lobar degeneration (FTLD) with ubiquitin-positive, tau-negative inclusions, and linkage to chromosome 17 was recently found to be caused by mutations in the progranulin (PGRN) gene. In this study, we screened a group of 51 FTLD patients for PGRN mutations and identified a novel exon 6 splice donor site deletion (IVS6+5_8delGTGA) in 2 unrelated patients. This mutation displayed an altered splicing pattern generating 2 aberrant transcripts and causing frameshifts of the coding sequence, premature termination codons, and a near absence of PGRN mRNA from the mutated alleles most likely through nonsense-mediated decay. The subsequent PGRN haploinsufficiency is consistent with previously described PGRN mutations. We present a molecular characterization of the IVS6+5_8delGTGA mutation and also describe clinical and neuropathologic features from the 2 patients carrying this PGRN mutation. From the screening of these 51 FTLD patients, we could also identify the earlier reported mutation Gln130fs, and several coding sequence variants that are most likely nonpathogenic.

Place, publisher, year, edition, pages
2011. Vol. 25, no 2, 173-178 p.
Keyword [en]
frontotemporal lobar degeneration, frontotemporal dementia, progranulin, ubiquitin, TDP-43
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-144814DOI: 10.1097/WAD.0b013e3181fbc22cISI: 000290787700012PubMedID: 20975516OAI: oai:DiVA.org:uu-144814DiVA: diva2:394480
Available from: 2011-02-02 Created: 2011-02-02 Last updated: 2012-01-26Bibliographically approved

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