Mutations of the MAPT (microtubule-associated protein tau) gene are associated with FTLD (frontotemporal lobar degeneration) with tau pathology. These mutations result in a decreased ability of tau to bind MTs (microtubules), an increased production of tau with four MT-binding repeats or enhanced tau aggregation. In two FTLD patients, we recently described CNVs (copy number variations) affecting the MAPT gene, consisting of a partial deletion and a complete duplication of the gene. The partial deletion resulted in a truncated protein lacking the first MT-binding domain, which had a dramatic decrease in the binding to MTs but acquired the ability to bind MAP (microtubule-associated protein) 1-B. In this case, tauopathy probably resulted from both a loss of normal function and a gain of function by which truncated tau would sequester another MAP. In the other FTLD patient, the complete duplication might result in the overexpression of tau, which in the mouse model induces axonopathy and tau aggregates reminiscent of FTLD-tau pathology. Interestingly, the same rearrangement was also described in several children with mental retardation, autism spectrum disorders and dysmorphic features, as well as in a schizophrenic patient. Finally, complete deletions of the MAPT gene have been associated with mental retardation, hypotonia and facial dysmorphism.
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Conference Article|
July 20 2012
Copy number variations involving the microtubule-associated protein tau in human diseases
Anne Rovelet-Lecrux;
Anne Rovelet-Lecrux
1
*Inserm, U1079, Rouen, France
†University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France
1To whom correspondence should be addressed (emailanne.roveletlecrux@univ-rouen.fr).
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Dominique Campion
Dominique Campion
*Inserm, U1079, Rouen, France
†University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France
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Publisher: Portland Press Ltd
Received:
February 24 2012
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (4): 672–676.
Article history
Received:
February 24 2012
Citation
Anne Rovelet-Lecrux, Dominique Campion; Copy number variations involving the microtubule-associated protein tau in human diseases. Biochem Soc Trans 1 August 2012; 40 (4): 672–676. doi: https://doi.org/10.1042/BST20120045
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