Partial deletion of the MAPT gene: a novel mechanism of FTDP-17
- PMID: 19263483
- DOI: 10.1002/humu.20979
Partial deletion of the MAPT gene: a novel mechanism of FTDP-17
Abstract
A heterozygous genomic deletion removing exons 6 to 9 of the microtubule associated protein tau (MAPT) gene, predicting to result into a truncated protein lacking the first microtubule binding domain, was detected in a patient with frontotemporal dementia (FTD). Cell culture experiments showed that the truncated tau isoforms had a dramatic decrease in the normal binding to microtubules but acquired the ability to bind microtubule associated protein-1B (MAP-1B). This indicates that this tauopathy likely results both from a loss of function mechanism and from a deleterious gain of function by which cytoplasmic deleted forms of tau sequester another MAP. Both mechanisms could contribute to impair microtubule dynamics.
(c) 2009 Wiley-Liss, Inc.
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