title: Association of the variant Cys139Arg at GRN gene to the clinical spectrum of frontotemporal lobar degeneration.
abstract: BACKGROUND
  Progranulin protein (PGRN) is a cysteine-rich growth factor encoded by the progranulin gene (GRN). PGRN mutations were identified in patients with frontotemporal lobar degeneration (FTLD) and recently its role as risk factor has been described in patients with probable Alzheimer's disease (AD). To date, more than 100 genetic variants in GRN gene have been described and the pathogenic nature is still unclear for almost 36% of them.
  
  
  OBJECTIVE
  Here, we describe three clinical cases carrying the PGRN variation Cys139Arg in order to increase the knowledge on the association of this variant to the clinical spectrum of FTLD.
  
  
  METHODS
  The genetic analysis was performed using high resolution melting analysis. The Human Progranulin ELISA Kit was used in order to determine PGRN expression levels in the plasma samples.
  
  
  RESULTS
  The three patients carrying the genetic variation showed three final different clinical diagnosis, respectively behavioral frontotemporal dementia, semantic dementia, and corticobasal syndrome, thus underlining the clinical heterogeneity typically associated with GRN mutations. All cases shared similar plasma PGRN levels that resulted intermediate between those measured in controls and in GRN null mutation carriers, showing a partial reduction of the protein in plasma. Moreover, according to the bioinformatics software, the Cys139Arg variation causes a decreased stability of the structure of the protein.
  
  
  CONCLUSIONS
  We describe three new patients affected by neurological syndromes included in the clinical spectrum of FTLD carrying the Cys139Arg genetic variant, thus suggesting a possible implication in the pathogenesis of FTLD.
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Irene
authors: I
authors: Piaceri
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Silvia
authors: S
authors: Pradella
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Chiara
authors: C
authors: Cupidi
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Serena
authors: S
authors: Nannucci
authors: Department of Clinical Pathophysiology, Nuclear Medicine Division, University of Florence, Florence, Italy.
authors: Cristina
authors: C
authors: Polito
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Silvia
authors: S
authors: Bagnoli
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Andrea
authors: A
authors: Tedde
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Nicoletta
authors: N
authors: Smirne
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Maria
authors: M
authors: Anfossi
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Maura
authors: M
authors: Gallo
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Livia
authors: L
authors: Bernardi
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Rosanna
authors: R
authors: Colao
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Raffaele
authors: R
authors: Maletta
authors: Centro Regionale di Neurogenetica, ASP Catanzaro, Lamezia Terme (CZ), Italy.
authors: Amalia Cecilia
authors: AC
authors: Bruni
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Sandro
authors: S
authors: Sorbi
authors: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy.
authors: Benedetta
authors: B
authors: Nacmias
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000235:genetics*; D003545:Cysteine / Q000235:genetics*; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D000077153:Progranulins
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D001120:Arginine; D003545:Cysteine
keywords: Cys139Arg; frontotemporal dementia; mutation; plasma; progranulin