Frontotemporal dementia phenotype associated with MAPT gene duplication.
Microduplications at 17q21.31 have recently been reported in children with mental retardation, autism spectrum disorders and/or dysmorphic features, as well as in a single schizophrenic patient. This rearrangement encompasses the microtubule associated protein tau (MAPT) gene, mutations of which are a major cause of frontotemporal lobar degeneration (FTLD). However, no 17q21.31 microduplication has been so far identified in this condition. We screened chromosomal rearrangements in FTLD patients using quantitative multiplex PCR of short fluorescent fragments and high resolution array CGH. We found a 439-kb microduplication at the 17q21.31 locus encompassing the MAPT, IMP5, CRHR1, and STH genes in the index case of a family in which three patients have developed a FTLD phenotype associated with marked memory impairment. None of these patients had mental retardation or dysmorphic features. Since no pathological examination was available, we are not certain that this case corresponds to a FTLD with neuronal and glial tau inclusions (FTLD-tau), and we cannot exclude that any other gene included in the rearrangement might be responsible for the neurodegenerative process. However, the clinical phenotype of the three patients is functionally consistent with the regional pattern of lesions previously reported in mice overexpressing human tau.
Rovelet-Lecrux
Anne
A
Inserm U614, Faculty Medicine, University of Rouen, Rouen, France.
Hannequin
Didier
D
Guillin
Olivier
O
Legallic
Solenn
S
Jurici
Snejana
S
Wallon
David
D
Frebourg
Thierry
T
Campion
Dominique
D
D000368:Aged; D001921:Brain / Q000473:pathology*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D020440:Gene Duplication; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016875:tau Proteins / Q000235:genetics*
C054369:MAPT protein, human; D016875:tau Proteins