title: C9orf72 repeat expansions are restricted to the ALS-FTD spectrum.
abstract: Expansion of a GGGGCC repeat (RE) in the C9orf72 gene has been recently reported as the main genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Given the growing evidence of genetic and clinicopathologic overlap among ALS, FTD, and other neurodegenerative diseases, we investigated the occurrence of RE in a subset of 9 patients with ALS-plus syndromes, including Parkinson's disease (PD), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy. We identified RE in 2 ALS-plus individuals (22.2%) displaying PSP and CBS features. On the basis of this finding, we extended our analysis to a cohort composed of 190 PD, 103 CBS, 107 PSP, and 177 Alzheimer's disease cases. We did not identify any RE in these patients, indicating that C9orf72 is in all probability not involved in the pathogenesis of these disorders. However, the high frequency of C9orf72 RE in patients with ALS-plus syndromes suggests that, similar to ALS-FTD patients, individuals with combined motor neuron and extrapyramidal features should be screened for RE, independent of their family history.
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy. Electronic address: n.ticozzi@auxologico.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ticozzi
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Doctoral School in Molecular Medicine, Department of Sciences and Biomedical Technologies, University of Milan, Milan, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Tiloca
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Calini
authors.affiliation: Laboratory of Experimental Neurology, Istituto di Ricovero e Cura a Carattere Scientifico C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Gagliardi
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Altieri
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Colombrita
authors.affiliation: Laboratory of Experimental Neurology, Istituto di Ricovero e Cura a Carattere Scientifico C. Mondino National Neurological Institute, Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Cereda
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Ratti
authors.affiliation: Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Pezzoli
authors.affiliation: Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.affiliation: Parkinson Institute, Istituti Clinici di Perfezionamento, Milan, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Goldwurm
authors.affiliation: Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.affiliation: Department of Neurology and Laboratory of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico Istituto Auxologico Italiano, Milan, Italy; Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Silani
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001480:Basal Ganglia Diseases / Q000235:genetics; D000073885:C9orf72 Protein; D015331:Cohort Studies; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons; D019578:Multiple System Atrophy / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics; D013577:Syndrome
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins
keywords: Amyotrophic lateral sclerosis; C9orf72; Corticobasal syndrome; Frontotemporal lobar degeneration; Neurogenetics; Progressive supranuclear palsy