Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/78583
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Type: | Journal article |
Title: | C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients |
Author: | Dobson-Stone, C. Hallupp, M. Loy, C. Thompson, E. Haan, E. Sue, C. Panegyres, P. Razquin, C. Seijo-Martinez, M. Ramon, R. Gascon, J. Campdelacreu, J. Schmoll, B. Volk, A. Brooks, W. Schofield, P. Pastor, P. Kwok, J. |
Citation: | PLoS One, 2013; 8(2):1-6 |
Publisher: | Public Library of Science |
Issue Date: | 2013 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Wider, C. |
Statement of Responsibility: | Carol Dobson-Stone, Marianne Hallupp, Clement T. Loy, Elizabeth M. Thompson, Eric Haan, Carolyn M. Sue, Peter K. Panegyres, Cristina Razquin, Manuel Seijo-Martínez, Ramon Rene, Jordi Gascon, Jaume Campdelacreu, Birgit Schmoll, Alexander E. Volk, William S. Brooks, Peter R. Schofield, Pau Pastor, John B. J. Kwok |
Abstract: | A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ~65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ~65 repeats may be sufficient to cause disease. |
Keywords: | Humans Proteins DNA Repeat Expansion Alleles Aged Middle Aged Australia Spain Female Male Frontotemporal Dementia C9orf72 Protein White People |
Rights: | © 2013 Dobson-Stone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
DOI: | 10.1371/journal.pone.0056899 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/630428 http://purl.org/au-research/grants/nhmrc/510217 http://purl.org/au-research/grants/nhmrc/630434 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0056899 |
Appears in Collections: | Aurora harvest Paediatrics publications |
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