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Partial deletion of the MAPT gene: A novel mechanism of FTDP‐17
Author(s) -
RoveletLecrux Anne,
Lecourtois Magalie,
ThomasAnterion Catherine,
Le Ber Isabelle,
Brice Alexis,
Frebourg Thierry,
Hannequin Didier,
Campion Dominique
Publication year - 2009
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20979
Subject(s) - biology , microtubule , exon , tauopathy , frontotemporal dementia , gene , tau protein , microtubule associated protein , gene isoform , mechanism (biology) , genetics , function (biology) , binding domain , microbiology and biotechnology , binding site , alzheimer's disease , dementia , neurodegeneration , medicine , philosophy , disease , epistemology , pathology
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. © 2009 Wiley‐Liss, Inc.