Document Detail

Novel progranulin mutation detected in 2 patients with FTLD.
MedLine Citation:
PMID:  20975516     Owner:  NLM     Status:  MEDLINE    
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.
Lena Skoglund; Toshifumi Matsui; Stefanie H Freeman; Anders Wallin; Elin S Blom; Matthew P Frosch; John H Growdon; Bradley T Hyman; Lars Lannfelt; Martin Ingelsson; Anna Glaser
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Alzheimer disease and associated disorders     Volume:  25     ISSN:  1546-4156     ISO Abbreviation:  Alzheimer Dis Assoc Disord     Publication Date:    2011 Apr-Jun
Date Detail:
Created Date:  2011-05-23     Completed Date:  2011-10-19     Revised Date:  2013-07-22    
Medline Journal Info:
Nlm Unique ID:  8704771     Medline TA:  Alzheimer Dis Assoc Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-8     Citation Subset:  IM    
Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
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MeSH Terms
DNA Mutational Analysis
Frontotemporal Lobar Degeneration / genetics*,  pathology
Intercellular Signaling Peptides and Proteins / genetics*
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
Reg. No./Substance:
0/GRN protein, human; 0/Intercellular Signaling Peptides and Proteins; 0/RNA, Messenger

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