TY - JOUR
T1 - C9orf72 repeat expansions are restricted to the ALS-FTD spectrum
AU - Ticozzi, Nicola
AU - Tiloca, Cinzia
AU - Calini, Daniela
AU - Gagliardi, Stella
AU - Altieri, Alessandra
AU - Colombrita, Claudia
AU - Cereda, Cristina
AU - Ratti, Antonia
AU - Pezzoli, Gianni
AU - Borroni, Barbara
AU - Goldwurm, Stefano
AU - Padovani, Alessandro
AU - Silani, Vincenzo
PY - 2014/4
Y1 - 2014/4
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - C9orf72
KW - Corticobasal syndrome
KW - Frontotemporal lobar degeneration
KW - Neurogenetics
KW - Progressive supranuclear palsy
UR - http://www.scopus.com/inward/record.url?scp=84891373809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84891373809&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2013.09.037
DO - 10.1016/j.neurobiolaging.2013.09.037
M3 - Article
C2 - 24169076
VL - 35
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 4
ER -