title: MAPT V363I variation in a sporadic case of frontotemporal dementia: variable penetrant mutation or rare polymorphism?
abstract: The V363I mutation of the microtubule-associated protein tau gene has previously been associated with a case of primary progressive nonfluent aphasia with variable penetrance. Herein, we report the finding of the V363I variation in a sporadic early onset frontotemporal dementia patient and in several members of her family. The V363I variation was associated with frontotemporal dementia only in the proband which was also homozygous for the A allele of the progranulin single-nucleotide polymorphism rs9897526 and for methionine at codon 129 of the prion protein gene. The microtubule-associated protein tau V363I variation could be considered either an incomplete penetrant mutation or a rare polymorphism; although its pathogenicity has yet to be clearly demonstrated, modifier genetic factors seem to contribute to the pathogenic effects observed in the patient underlining the great complexity existing in neurodegenerative diseases and questioning so-called sporadic cases that can potentially be caused by gene mutation.
authors.affiliation: Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.forename: Livia
authors.initials: L
authors.lastname: Bernardi
authors.forename: Maura
authors.initials: M
authors.lastname: Gallo
authors.forename: Silvana
authors.initials: S
authors.lastname: Geracitano
authors.forename: Rosanna
authors.initials: R
authors.lastname: Colao
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puccio
authors.forename: Sabrina A M
authors.initials: SA
authors.lastname: Curcio
authors.forename: Francesca
authors.initials: F
authors.lastname: Frangipane
authors.forename: Maria
authors.initials: M
authors.lastname: Mirabelli
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomaino
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Smirne
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maletta
authors.forename: Amalia Cecilia
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; D016875:tau Proteins