title: Novel MAPT Val75Ala mutation and PSEN2 Arg62Hys in two siblings with frontotemporal dementia.
abstract: A clinical and molecular overlap between Alzheimer's disease (AD) and frontotemporal dementia (FTD) has been reported. Presenilins have been associated with FTD or with FTD-like phenotype, while mutations in the MAPT gene have been linked to a clinical phenotype of AD. We performed a clinical and genetic examination in two FTD siblings and their family tree has been reconstructed. We identified a novel Val75Ala MAPT mutation in one patient and in the other the Arg62His Presenilin2 mutation. The DNA variations identified, defined mutations by frequency, per se are not causative of the disease. These mutations, possibly in association with other unknown environmental and genetic factors, may contribute to neurodegeneration. In this family, the disease might result from a genetically interconnected spectrum of altered pathways that could link most neurodegenerative disorders. Moreover, the novel mutation identified merits further functional studies that would contribute to the unravelling of such a complex field.
authors.affiliation: Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 88046, Lamezia Terme (CZ), Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Gallo
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomaino
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puccio
authors.forename: Francesca
authors.initials: F
authors.lastname: Frangipane
authors.forename: Sabrina A M
authors.initials: SA
authors.lastname: Curcio
authors.forename: Livia
authors.initials: L
authors.lastname: Bernardi
authors.forename: Silvana
authors.initials: S
authors.lastname: Geracitano
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.forename: Maria
authors.initials: M
authors.lastname: Mirabelli
authors.forename: Rosanna
authors.initials: R
authors.lastname: Colao
authors.forename: Franca
authors.initials: F
authors.lastname: Vasso
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Smirne
authors.forename: Raffaele G
authors.initials: RG
authors.lastname: Maletta
authors.forename: Amalia Cecilia
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D000328:Adult; D017668:Age of Onset; D005190:Family; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D053766:Presenilin-2 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings; D016875:tau Proteins / Q000235:genetics*
chemical_list: C054369:MAPT protein, human; C508861:PSEN2 protein, human; D053766:Presenilin-2; D016875:tau Proteins