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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: 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.
GLOSSARY
- 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
Footnotes
Coinvestigators and Contributors are listed on the Neurology® Web site at www.neurology.org.
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).
Supplemental data at www.neurology.org
- Received April 27, 2012.
- Accepted June 29, 2012.
- Copyright © 2012 by AAN Enterprises, Inc.
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