| Title |
A novel tau mutation, p.K317N, causes globular glial tauopathy
|
|---|---|
| Published in |
Acta Neuropathologica, April 2015
|
| DOI | 10.1007/s00401-015-1425-0 |
| Pubmed ID | |
| Authors |
Pawel Tacik, Michael DeTure, Wen-Lang Lin, Monica Sanchez Contreras, Aleksandra Wojtas, Kelly M. Hinkle, Shinsuke Fujioka, Matthew C. Baker, Ronald L. Walton, Yari Carlomagno, Patricia H. Brown, Audrey J. Strongosky, Naomi Kouri, Melissa E. Murray, Leonard Petrucelli, Keith A. Josephs, Rosa Rademakers, Owen A. Ross, Zbigniew K. Wszolek, Dennis W. Dickson |
| Abstract |
Globular glial tauopathies (GGTs) are 4-repeat tauopathies neuropathologically characterized by tau-positive, globular glial inclusions, including both globular oligodendroglial inclusions and globular astrocytic inclusions. No mutations have been found in 25 of the 30 GGT cases reported in the literature who have been screened for mutations in microtubule associated protein tau (MAPT). In this report, six patients with GGT (four with subtype III and two with subtype I) were screened for MAPT mutations. They included 4 men and 2 women with a mean age at death of 73 years (55-83 years) and mean age at symptomatic onset of 66 years (50-77 years). Disease duration ranged from 5 to 14 years. All were homozygous for the MAPT H1 haplotype. Three patients had a positive family history of dementia, and a novel MAPT mutation (c.951G>C, p.K317N) was identified in one of them, a patient with subtype III. Recombinant tau protein bearing the lysine-to-asparagine substitution at amino acid residue 317 was used to assess functional significance of the variant on microtubule assembly and tau filament formation. Recombinant p.K317N tau had reduced ability to promote tubulin polymerization. Recombinant 3R and 4R tau bearing the p.K317N mutation showed decreased 3R tau and increased 4R tau filament assembly. These results strongly suggest that the p.K317N variant is pathogenic. Sequencing of MAPT should be considered in patients with GGT and a family history of dementia or movement disorder. Since several individuals in our series had a positive family history but no MAPT mutation, genetic factors other than MAPT may play a role in disease pathogenesis. |
Mendeley readers
The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 3% |
| Unknown | 35 | 97% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 6 | 17% |
| Other | 5 | 14% |
| Student > Doctoral Student | 5 | 14% |
| Student > Bachelor | 3 | 8% |
| Professor > Associate Professor | 3 | 8% |
| Other | 5 | 14% |
| Unknown | 9 | 25% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 8 | 22% |
| Agricultural and Biological Sciences | 7 | 19% |
| Medicine and Dentistry | 5 | 14% |
| Biochemistry, Genetics and Molecular Biology | 3 | 8% |
| Psychology | 2 | 6% |
| Other | 1 | 3% |
| Unknown | 10 | 28% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 April 2015.
All research outputs
#4,173,376
of 22,800,560 outputs
Outputs from Acta Neuropathologica
#959
of 2,369 outputs
Outputs of similar age
#53,327
of 265,536 outputs
Outputs of similar age from Acta Neuropathologica
#24
of 38 outputs
Altmetric has tracked 22,800,560 research outputs across all sources so far. Compared to these this one has done well and is in the 80th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,369 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. This one has gotten more attention than average, scoring higher than 56% of its peers.
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