title: Novel PSEN1 and PGRN mutations in early-onset familial frontotemporal dementia.
abstract: 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.
authors.affiliation: Regional Neurogenetic Centre, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Bernardi
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomaino
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.forename: Maura
authors.initials: M
authors.lastname: Gallo
authors.forename: Silvana
authors.initials: S
authors.lastname: Geracitano
authors.forename: Angela
authors.initials: A
authors.lastname: Costanzo
authors.forename: Rosanna
authors.initials: R
authors.lastname: Colao
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: Maria
authors.initials: M
authors.lastname: Mirabelli
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Smirne
authors.forename: David
authors.initials: D
authors.lastname: Iapaolo
authors.forename: Raffaele Giovanni
authors.initials: RG
authors.lastname: Maletta
authors.forename: Amalia C
authors.initials: AC
authors.lastname: Bruni
mesh_terms: 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
chemical_list: 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