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Figure.  Results of a Survey Conducted on Genetic Testing Among Members of the Northeast ALS Consortium (n = 41)
Results of a Survey Conducted on Genetic Testing Among Members of the Northeast ALS Consortium (n = 41)

Percentage of respondents who reported testing for each gene specified in the survey. The total number of respondents who reported testing for specific ALS genes was 41 (of 43 who responded to the survey).

Table.  Survey Questions and Responses of Neurologists Who Study Amyotrophic Lateral Sclerosis (ALS) (N = 43)
Survey Questions and Responses of Neurologists Who Study Amyotrophic Lateral Sclerosis (ALS) (N = 43)
1.
Benatar  M, Stanislaw  C, Reyes  E,  et al.  Presymptomatic ALS genetic counseling and testing: experience and recommendations.  Neurology. 2016;86(24):2295-2302.PubMedGoogle ScholarCrossref
2.
Chiò  A, Battistini  S, Calvo  A,  et al; ITALSGEN Consortium.  Genetic counselling in ALS: facts, uncertainties and clinical suggestions.  J Neurol Neurosurg Psychiatry. 2014;85(5):478-485.PubMedGoogle ScholarCrossref
3.
Byrne  S, Elamin  M, Bede  P, Hardiman  O.  Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.  J Neurol Neurosurg Psychiatry. 2012;83(4):365-367.PubMedGoogle ScholarCrossref
Research Letter
January 2017

Use of Genetic Testing in Amyotrophic Lateral Sclerosis by Neurologists

Author Affiliations
  • 1Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland
  • 2The Northeast ALS Consortium, Boston, Massachusetts
  • 3’Rita Levi Montalcini’ Department of Neuroscience, University of Torino, Turin, Italy
JAMA Neurol. 2017;74(1):125-126. doi:10.1001/jamaneurol.2016.4540

There have been a number of publications describing the important role of genetic counseling in amyotrophic lateral sclerosis (ALS).1,2 While such attempts at guiding who should undergo genetic testing are welcome, they are put forth in a vacuum because there are no data on where ALS neurologists stand in terms of genetic testing and counseling for the disease, and in terms of what is considered to be familial and sporadic ALS.3 We attempted to fill this gap by surveying members of the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS, http://www.alsconsortium.org), one of the largest clinical research organizations for ALS.

We sought to understand in which situations genetic testing is used, which genes are tested for, and the attitudes of respondents toward genetic testing and counseling.

Methods

The survey was sent via email on June 20, 2016, to 134 principal investigators who are members of NEALS. The deadline for survey completion was July 29, 2016. Data were collated and analyzed using Microsoft Excel (Table). The NIH Office of Human Subjects Research Protection has determined that this type of research falls under exemption for institutional review board approval.

Results

We obtained 43 responses, resulting in a response rate of nearly one-third (32.1%). Responses were obtained from centers throughout the United States as well as from Canada, Israel, and Lebanon. The mean annual number of ALS patients seen at each site was 157 (range, 20-500). Forty respondents (93.0%) reported that they screen familial ALS cases for genetic mutations in their routine clinical practice and 13 (30.2%) screen sporadic cases. Genetic testing rates are surprisingly lower in the context of clinical research: only 31 respondents (72.1%) reported that they screen familial ALS cases for genetic mutations in preparation for their enrollment in clinical trials, while only 8 (18.6%) screen sporadic cases in clinical trials.

One respondent did not perform genetic testing for clinical trials or everyday clinical practice, and 1 respondent did not specify which genes the site tested for. Of the 41 respondents who specified which genes were tested for, 100% screened for C9ORF72 (Figure). The next most common gene screened for was SOD1, with 31 respondents (75.6%). Other genes reported are shown, by prevalence in testing, in the Figure. Of note, 2 respondents reported testing for Ataxin 2 in addition to other genes.

Just fewer than half of respondents (n = 21; 48.8%) reported using next-generation sequencing techniques at their sites. More than half of respondents (n = 24; 55.8%) reported using panel testing. Only 14 of the 24 respondents (58.3%) who reported using Sanger sequencing-based panel testing believed it to be cost-effective. Most respondents (n = 42; 97.7%) provide genetic counseling to ALS patients, with only 1 respondent denying the use of genetic counseling. Finally, the overwhelming majority of respondents (n = 39; 90.7%) would change their attitude toward genetic testing if an effective therapy for ALS became available.

Discussion

The importance of genetic testing in ALS is shown by the response to the question on whether future gene therapy trials will influence the practice of genetic testing. Almost uniformly the answer was yes. Our data show that although current efforts at genetic counseling guidelines for ALS patients are important, the pace of discovery in the genetic field means that these guidelines have a relatively short shelf life. Guideline documents need to operate in a dynamic manner with yearly updates, rather than being viewed as dogma.

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Article Information

Corresponding Author: Bryan J. Traynor, MD, PhD, Neuromuscular Diseases Research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892 (traynorb@mail.nih.gov).

Published Online: November 21, 2016. doi:10.1001/jamaneurol.2016.4540

Author Contributions: Dr Traynor had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Arthur, Chiò, Traynor.

Acquisition, analysis, or interpretation of data: Arthur, Doyle, Traynor.

Drafting of the manuscript: Arthur, Doyle, Chiò.

Critical revision of the manuscript for important intellectual content: Arthur, Chiò, Traynor.

Statistical analysis: Arthur, Traynor.

Obtained funding: Traynor.

Administrative, technical, or material support: Doyle, Traynor.

Conflict of Interest Disclosures: Dr Traynor has received research-funding support from Microsoft Research, Merck Inc, the Muscular Dystrophy Association, the ALS Association, the Myasthenia Gravis Foundation, and the Centers for Disease Control and Prevention. Dr Traynor has a patent pending on the clinical testing and therapeutic intervention for the hexanucleotide repeat expansion of C9orf72. No other disclosures were reported.

Funding/Support: This work was supported in part by the Intramural Research Program of the US National Institutes of Health (NIH), National Institute on Aging (grant Z01-AG000949-02). This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, The American Association for Dental Research, The Howard Hughes Medical Institute, and the Colgate-Palmolive Company, as well as other private donors. For a complete list, please visit the Foundation website at http://fnih.org/about/financials. This work was supported in part by the European Community’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867), the Joint Programme-Neurodegenerative Disease Research (Italian Ministry of Education and University) (Strength Project), and the Vialli and Mauro Foundation for ALS (grant No. 4).

Role of the Funder/Sponsor: The funding organizations had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication

Additional Contributions: We would like to thank NEALS and the neurologists who responded to the survey.

References
1.
Benatar  M, Stanislaw  C, Reyes  E,  et al.  Presymptomatic ALS genetic counseling and testing: experience and recommendations.  Neurology. 2016;86(24):2295-2302.PubMedGoogle ScholarCrossref
2.
Chiò  A, Battistini  S, Calvo  A,  et al; ITALSGEN Consortium.  Genetic counselling in ALS: facts, uncertainties and clinical suggestions.  J Neurol Neurosurg Psychiatry. 2014;85(5):478-485.PubMedGoogle ScholarCrossref
3.
Byrne  S, Elamin  M, Bede  P, Hardiman  O.  Absence of consensus in diagnostic criteria for familial neurodegenerative diseases.  J Neurol Neurosurg Psychiatry. 2012;83(4):365-367.PubMedGoogle ScholarCrossref
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