Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia.
BACKGROUND
Frontotemporal dementia is a clinically and genetically heterogeneous syndrome. Mutations in two genes, Microtubule Associated Protein Tau (MAPT) and Progranulin (PGRN), and rarely Presenilin mutations, have been causally linked to this disorder.


OBJECTIVE
To investigate the presence of PGRN, PSEN1, PSEN2 and APP mutations in a group of familial early-onset frontotemporal dementia (f-EOFTD) patients negative for MAPT gene mutations.


METHODS
We prospectively studied 17 unrelated subjects diagnosed with f-EOFTD (one case neuropathologically confirmed as FTD-Ub+). Among these subjects eight belonged to eight autosomal dominant families unrelated to each other, and nine had at least one first degree relative affected by dementia.


RESULTS
We identified two novel heterozygous mutations in two unrelated patients, Cys139Arg in the PGRN gene and Val412Ile in the PSEN1 gene.


CONCLUSIONS
Early-onset f-FTD remains a heterogeneous disorder from a genetic point of view. PGRN mutation frequency was low in our sample. The presence of a novel PSEN1 mutation suggests that presenilin molecular studies should be performed when screening for MAPT and PGRN genes is negative.
Bernardi
Livia
L
Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme (CZ), Italy.
Tomaino
Carmine
C
Anfossi
Maria
M
Gallo
Maura
M
Geracitano
Silvana
S
Costanzo
Angela
A
Colao
Rosanna
R
Puccio
Gianfranco
G
Frangipane
Francesca
F
Curcio
Sabrina A M
SA
Mirabelli
Maria
M
Smirne
Nicoletta
N
Iapaolo
David
D
Maletta
Raffaele Giovanni
RG
Bruni
Amalia C
AC
D000328:Adult; D001120:Arginine / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D019788:Fluorodeoxyglucose F18; D057180:Frontotemporal Dementia / Q000000981:diagnostic imaging / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053764:Presenilin-1 / Q000235:genetics*; D000077153:Progranulins; D011877:Radionuclide Imaging
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D000077153:Progranulins; D019788:Fluorodeoxyglucose F18; D001120:Arginine; D003545:Cysteine