dc.contributor.author |
Smith, BN |
en |
dc.contributor.author |
Vance, C |
en |
dc.contributor.author |
Scotter, Emma |
en |
dc.contributor.author |
Troakes, C |
en |
dc.contributor.author |
Wong, CH |
en |
dc.contributor.author |
Topp, S |
en |
dc.contributor.author |
Maekawa, S |
en |
dc.contributor.author |
King, A |
en |
dc.contributor.author |
Mitchell, JC |
en |
dc.contributor.author |
Lund, K |
en |
dc.contributor.author |
Al-Chalabi, A |
en |
dc.contributor.author |
Ticozzi, N |
en |
dc.contributor.author |
Silani, V |
en |
dc.contributor.author |
Sapp, P |
en |
dc.contributor.author |
Brown Jr., RH |
en |
dc.contributor.author |
Landers, JE |
en |
dc.contributor.author |
Al-Sarraj, S |
en |
dc.contributor.author |
Shaw, CE |
en |
dc.date.accessioned |
2015-08-17T02:09:07Z |
en |
dc.date.issued |
2015 |
en |
dc.identifier.citation |
Neurobiology of Aging, 2015, 36 (3), pp. 1602.e17 - 1602.e27 |
en |
dc.identifier.issn |
0197-4580 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/26736 |
en |
dc.description.abstract |
Abstract Mutations in the gene encoding Profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n=485) and detected 2 novel variants (A20T and Q139L) as well as 4 cases with the previously identified E117G rare variant (∼1.2%). A case-control meta-analysis of all published E117G ALS+/-FTD cases including those identified in this report was significant p=0.001, OR=3.26 (95% CI 1.6-6.8), demonstrating this variant to be a susceptibility allele. Post-mortem tissue from available patients displayed classic TDP-43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease. |
en |
dc.relation.ispartofseries |
Neurobiology of Aging |
en |
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. Details obtained from http://www.sherpa.ac.uk/romeo/issn/0197-4580/ |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.subject |
Amyotrophic lateral sclerosis |
en |
dc.subject |
Profilin 1 |
en |
dc.subject |
TDP-43 proteinopathy |
en |
dc.title |
Novel mutations support a role for Profilin1 in the pathogenesis of ALS |
en |
dc.type |
Journal Article |
en |
dc.identifier.doi |
10.1016/j.neurobiolaging.2014.10.032 |
en |
pubs.issue |
3 |
en |
pubs.begin-page |
1602.e17 |
en |
pubs.volume |
36 |
en |
dc.identifier.pmid |
25499087 |
en |
pubs.author-url |
http://www.sciencedirect.com/science/article/pii/S0197458014006927 |
en |
pubs.end-page |
1602.e27 |
en |
dc.rights.accessrights |
http://purl.org/eprint/accessRights/RestrictedAccess |
en |
pubs.subtype |
Article |
en |
pubs.elements-id |
460474 |
en |
pubs.org-id |
Science |
en |
pubs.org-id |
Biological Sciences |
en |
dc.identifier.eissn |
1558-1497 |
en |
pubs.record-created-at-source-date |
2014-11-10 |
en |
pubs.dimensions-id |
25499087 |
en |