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The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features.

Kara, E; Ling, H; Pittman, AM; Shaw, K; de Silva, R; Simone, R; Holton, JL; ... Revesz, T; + view all (2012) The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features. Neurobioly of Aging , 33 (9) 2231.e7 - 2231.e14. 10.1016/j.neurobiolaging.2012.04.006. Green open access

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Abstract

Microtubule-associated protein tau (MAPT) mutations have been shown to underlie frontotemporal dementia and a variety of additional sporadic tauopathies. We identified a rare p.A152T variant in MAPT exon 7 in two (of eight) patients with clinical presentation of parkinsonism and postmortem finding of neurofibrillary tangle pathology. Two siblings of one patient also carried the p.A152T variant, and both have progressive cognitive impairment. Further screening identified the variant in two other cases: one with pathologically confirmed corticobasal degeneration and another with the diagnosis of Parkinson's disease with dementia. The balance of evidence suggests this variant is associated with disease, but the very varied phenotype of the cases with the mutation is not consistent with it being a fully penetrant pathogenic mutation. Interestingly, this variation results in the creation of a new phosphorylation site that could cause reduced microtubule binding. We suggest that the A152T variant is a risk factor associated with the development of atypical neurodegenerative conditions with abnormal tau accumulation.

Type: Article
Title: The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features.
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neurobiolaging.2012.04.006
Publisher version: http://dx.doi.org/10.1016/j.neurobiolaging.2012.04...
Language: English
Additional information: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3657164
Keywords: Aged, 80 and over, Brain, DNA Mutational Analysis, DNA-Binding Proteins, Female, Humans, Melanins, Middle Aged, Mutation, Nervous System Diseases, Neurofilament Proteins, Risk Factors, Tauopathies, tau Proteins
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: http://discovery.ucl.ac.uk/id/eprint/1348337
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