title: Novel N-terminal domain mutation in prion protein detected in 2 patients diagnosed with frontotemporal lobar degeneration syndrome.
abstract: Prion protein gene mutations have been associated with clinical pictures mimicking neurodegenerative diseases different from inherited prion diseases (IPD). We report a novel missense P39L mutation in the N-terminal domain of prion protein in 2 patients affected by frontotemporal lobar degeneration syndrome, negative for mutations in genes causative of dementia. Neither the first carrier, a 67-year-old male in which the onset was a progressive non-fluent aphasia, nor the second carrier, a 78-year-old male affected by frontotemporal dementia and parkinsonism, showed any clinical or instrumental findings suggestive of IPD. Genetic screening of healthy controls and in silico analysis provide support for the potential pathogenicity of this variant. Patient phenotypes, unclassifiable as prion disease, may depend on the location of the mutation in the N-terminal domain, outside the amyloid core of pathologic prion protein, although further functional studies are required to determine whether and how this mutation exerts its pathogenic effect. However, genetic screening of prion protein gene becomes relevant in familial degenerative dementia, particularly in geographical areas with high IPD prevalence.
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Bernardi
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cupidi
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Frangipane
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Anfossi
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Gallo
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Conidi
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Franca
authors.initials: F
authors.lastname: Vasso
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Colao
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Puccio
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Sabrina A M
authors.initials: SAM
authors.lastname: Curcio
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Mirabelli
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Clodomiro
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Di Lorenzo
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Smirne
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Maletta
authors.affiliation: Regional Neurogenetic Centre, ASP CZ, Lamezia Terme, Catanzaro, Italy. Electronic address: bruni@arn.it.
authors.forename: Amalia C
authors.initials: AC
authors.lastname: Bruni
mesh_terms: D000368:Aged; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000175:diagnosis* / Q000235:genetics*; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D011328:Prions / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D013577:Syndrome
chemical_list: D011328:Prions
keywords: Frontotemporal dementia; N-terminal domain; P39L mutation; Prion protein