RT Journal Article
SR Electronic
T1 Extensive genetics of ALS
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP 1983
OP 1989
DO 10.1212/WNL.0b013e3182735d36
VO 79
IS 19
A1 Chiò, Adriano
A1 Calvo, Andrea
A1 Mazzini, Letizia
A1 Cantello, Roberto
A1 Mora, Gabriele
A1 Moglia, Cristina
A1 Corrado, Lucia
A1 D'Alfonso, Sandra
A1 Majounie, Elisa
A1 Renton, Alan
A1 Pisano, Fabrizio
A1 Ossola, Irene
A1 Brunetti, Maura
A1 Traynor, Bryan J.
A1 Restagno, Gabriella
YR 2012
UL http://n.neurology.org/content/79/19/1983.abstract
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: The study population includes all ALS cases diagnosed in Piemonte, Italy, from January 2007 to June 2011. Mutations of SOD1, TARDBP, ANG, FUS, OPTN, and C9ORF72 have 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. ALS=amyotrophic lateral sclerosis; bvFTD=behavioral variant frontotemporal dementia; CI=confidence interval; fALS=familial ALS; FTD=frontotemporal dementia; OR=odds ratio; PARALS=Piemonte and Valle d'Aosta register for ALS; sALS=sporadic ALS