This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.
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.
AAN Members
We have changed the login procedure to improve access between AAN.com and the Neurology journals. If you are experiencing issues, please log out of AAN.com and clear history and cookies. (For instructions by browser, please click the instruction pages below). After clearing, choose preferred Journal and select login for AAN Members. You will be redirected to a login page where you can log in with your AAN ID number and password. When you are returned to the Journal, your name should appear at the top right of the page.
AAN Non-Member Subscribers
Purchase access
Letters: Rapid online correspondence
REQUIREMENTS
You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.
Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.
If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.
Submission specifications:
- Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
- Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
- Submit only on articles published within 6 months of issue date.
- Do not be redundant. Read any comments already posted on the article prior to submission.
- Submitted comments are subject to editing and editor review prior to posting.
You May Also be Interested in
Association of Neurofilament Light With the Development and Severity of Parkinson Disease
Dr. Rodolfo Savica and Dr. Parichita Choudhury
► Watch
Topics Discussed
Alert Me
Recommended articles
Phenotype and genotype analysis in amyotrophic lateral sclerosis with TARDBP gene mutations
Conjoint pathologic cascades mediated by ALS/FTLD-U linked RNA-binding proteins TDP-43 and FUS
Unraveling ALS due to SOD1 mutation through the combination of brain and cervical cord MRI
Genetics of familial amyotrophic lateral sclerosis