TY - JOUR
T1 - Extensive genetics of ALS
T2 - A population-based study in Italy
AU - Chio, Adriano
AU - Calvo, Andrea
AU - Mazzini, Letizia
AU - Cantello, Roberto
AU - Mora, Gabriele
AU - Moglia, Cristina
AU - Corrado, Lucia
AU - D'Alfonso, Sandra
AU - Majounie, Elisa
AU - Renton, Alan
AU - Pisano, Fabrizio
AU - Ossola, Irene
AU - Brunetti, Maura
AU - Traynor, Bryan J.
AU - Restagno, Gabriella
N1 - Funding Information:
Study funding: This work was funded in part by Federazione Italiana Giuoco Calcio, Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus, Ministero della Salute (Ricerca Sanitaria Finalizzata, 2007), Regione Piemonte (Progetti Finalizzati 2003 and 2004), Associazione Amico Canobio, Fondazione Cariplo (no. 2010–0728), and PRIN 2008. The research leading to these results has received funding from the European Community's Health Seventh Framework Programme (FP7/2007–2013) (grant agreements no. 259867 and 278611) . This work was supported in part by the Intramural Research Programs of the NIH, National Institute on Aging (Z01-AG000949–02).
Funding Information:
A. Chiò has received research support from Italian Ministry of Health (Ricerca Finalizzata), Regione Piemonte (Ricerca Finalizzata), University of Torino, Federazione Italiana Giuoco Calcio, Fondazione Vialli e Mauro onlus, and European Commission (Health Seventh Framework Programme), and serves on a scientific advisory board for Biogen Idec and Cytokinetics. A. Calvo has received research support from Regione Piemonte (Ricerca Finalizzata) and Compagnia di San Paolo. L. Mazzini has received research support from Fondazione Borgonovo. R. Cantello reports no disclosures. G. Mora has received research support from Italian Ministry of Health (Ricerca Finalizzata). C. Moglia and L. Corrado report no disclosures. S. D'Alfonso has received research support from Fondazione Cariplo. E. Majunie, A. Renton, F. Pisano, I. Ossola, M. Brunetti, and B. Traynor report no disclosures. G. Restagno reports has received research support from Italian Ministry of Health (Ricerca Finalizzata) and Regione Piemonte (Ricerca Finalizzata). Go to Neurology.org for full disclosures.
PY - 2012/11/6
Y1 - 2012/11/6
N2 - Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: Thestudy population includes allALScases diagnosed in Piemonte, Italy, from January2007to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, andC9ORF72have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that ̃11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease.
AB - Objective: To assess the frequency and clinical characteristics of patients with mutations of major amyotrophic lateral sclerosis (ALS) genes in a prospectively ascertained, population-based epidemiologic series of cases. Methods: Thestudy population includes allALScases diagnosed in Piemonte, Italy, from January2007to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, andC9ORF72have been assessed. Results: Out of the 475 patients included in the study, 51 (10.7%) carried a mutation of an ALS-related gene (C9ORF72, 32; SOD1, 10; TARDBP, 7; FUS, 1; OPTN, 1; ANG, none). A positive family history for ALS or frontotemporal dementia (FTD) was found in 46 (9.7%) patients. Thirty-one (67.4%) of the 46 familial cases and 20 (4.7%) of the 429 sporadic cases had a genetic mutation. According to logistic regression modeling, besides a positive family history for ALS or FTD, the chance to carry a genetic mutation was related to the presence of comorbid FTD (odds ratio 3.5; p = 0.001), and age at onset ≤54 years (odds ratio 1.79; p = 0.012). Conclusions: We have found that ̃11% of patients with ALS carry a genetic mutation, with C9ORF72 being the commonest genetic alteration. Comorbid FTD or a young age at onset are strong indicators of a possible genetic origin of the disease.
UR - https://www.scopus.com/pages/publications/84871192467
U2 - 10.1212/WNL.0b013e3182735d36
DO - 10.1212/WNL.0b013e3182735d36
M3 - Article
SN - 0028-3878
VL - 79
SP - 1983
EP - 1989
JO - Neurology
JF - Neurology
IS - 19
ER -