Novel MAPT Val75Ala mutation and PSEN2 Arg62Hys in two siblings with frontotemporal dementia.
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.
Gallo
Maura
M
Centro Regionale di Neurogenetica, Azienda Sanitaria Provinciale Catanzaro, Viale A. Perugini, 88046, Lamezia Terme (CZ), Italy.
Tomaino
Carmine
C
Puccio
Gianfranco
G
Frangipane
Francesca
F
Curcio
Sabrina A M
SA
Bernardi
Livia
L
Geracitano
Silvana
S
Anfossi
Maria
M
Mirabelli
Maria
M
Colao
Rosanna
R
Vasso
Franca
F
Smirne
Nicoletta
N
Maletta
Raffaele G
RG
Bruni
Amalia Cecilia
AC
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*
C054369:MAPT protein, human; C508861:PSEN2 protein, human; D053766:Presenilin-2; D016875:tau Proteins