Abstract Details

Title Genetic Testing for ALS: The Incidence of Pathogenic, Likely Pathogenic, and Uncertain Variants in a Clinic-Based Population

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 1-013

Objective 1) To determine the incidence of pathogenic (P) and likely pathogenic (LP) variants in a prospective clinic-based ALS cohort at an academic medical center, using a testing algorithm based on family history and age of onset 2) To compare the incidence of P or LP variants in fALS, dALS (ALS patients with a family history of dementia), sALS (having no known family history of ALS or dementia), and in early onset cases (onset <50 years of age).

Background A genetic etiology has been reported in 70% of familial ALS and 15% of sporadic ALS, in research cohorts. However, no data are available on the yield of clinical genetic testing in clinic-based ALS populations.

Design/Methods We report genetic testing outcomes of 167 patients in a tertiary care ALS clinic, using an algorithm based on family history and age of onset.

Results The incidence of P (pathogenic) or LP (likely pathogenic) variants was 56.0% in fALS (familial ALS); 11.8% in dALS (ALS patients with a family history of dementia), and 6.8% in sALS (sporadic ALS). P or LP variants were detected in 18.5% of early onset cases. Our data suggests that the incidence of P and LP variants in genes other than C9orf72 is lower than expected in Midwestern fALS cases, compared to research cohorts.

Conclusions

We advocate the offer of C9orf72 testing to all persons with ALS, and multigene testing as a second step for those with fALS or onset of symptoms before the age of 50 years. However, the incidence of P or LP variants in genes other than C9orf72 (including SOD1) may be lower than expected from published research cohorts. An accurate understanding of the incidence of pathogenic variants in clinic-based ALS populations is necessary to prioritize targets for therapeutic intervention and inform clinical trial design.

Authors/Disclosures
Jennifer A. Roggenbuck, MS, CGC (Ohio State University) PRESENTER	The institution of Ms. Roggenbuck has received research support from Packard Foundation.
	No disclosure on file
	No disclosure on file
Adam Quick, MD (The Ohio State University)	The institution of Dr. Quick has received research support from NINDS. The institution of Dr. Quick has received research support from NEALS.
Stephen J. Kolb, MD, PhD (The Ohio State University)	Dr. Kolb has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for AveXis. Dr. Kolb has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CureSMA. The institution of Dr. Kolb has received research support from NIH. The institution of Dr. Kolb has received research support from AveXis. The institution of Dr. Kolb has received research support from NIH.

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