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 January2007 to 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.

Extensive genetics of ALS: A population-based study in Italy

CHIO', Adriano;CALVO, Andrea;MOGLIA, CRISTINA;BRUNETTI, Maura;
2012-01-01

Abstract

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 January2007 to 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.
73
1983
1989
Amyotrophic lateral sclerosis; genetics; epidemiology
Chiò A; Calvo A; Mazzini L; Cantello R; Mora G; Moglia C; Corrado L; D'Alfonso S; Majounie E; Renton A; Pisano F; Ossola I; Brunetti M; Traynor BJ; Restagno G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/126711
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