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Abstract Details

The ALS Genetic Access Program: Paving the Way for Genetic Testing, Counseling and Therapy for ALS
Neuromuscular and Clinical Neurophysiology (EMG)
Neuromuscular and Clinical Neurophysiology (EMG) Posters (7:00 AM-5:00 PM)
030
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Although a genetic etiology can now be found in 75% of familial and 10% of sporadic ALS, clinical testing practices are inconsistent. As gene-targeted clinical trials begin, there is a need to increase access to ALS genetic testing in order to determine genetic causes of ALS in clinic-based populations and identify candidates for clinical trials.
A clinical cohort of ALS patients was tested in the ALS Genetic Access Program, a pilot genetic testing and counseling program of the Northeast ALS Consortium. Patients with a family history of ALS (fALS) or dementia (dALS) were tested for the C9orf72 hexanucleotide repeat expansion (HRE). fALS patients who tested negative for the HRE were then tested for 5 additional genes via a targeted panel: SOD1, FUS, TARDBP, TBK1, and VCP.
Testing has been completed in 573 patients; ~1 in 3 received a positive genetic diagnosis with 24% (137/573) positive for the HRE and 6% (34/573) positive for a pathogenic or likely pathogenic variant in one of the five panel genes. Use of a targeted, 5-gene panel resulted in a somewhat lower diagnostic yield in fALS cases as compared to published yields of larger panels (47% vs 56%), but with far fewer uncertain outcomes (7% vs 35%). Patients with earlier ages of onset and with stronger family histories of ALS were more likely to test positive.  Caucasian patients were more likely to test positive for the HRE, while non-Caucasians had a greater proportion of positive results on panel testing.
Test outcome data from this cohort, the largest to undergo standardized clinical ALS genetic testing and interpretation, confirm C9orf72 HRE as by far the most frequent pathogenic ALS variant identified in clinical practice and emphasize its importance as a therapeutic target. These data may contribute to development of uniform approaches to genetic testing for ALS.
Authors/Disclosures
Kelly Rich, MS, CGC
PRESENTER 		Ms. Rich has nothing to disclose.
Jennifer A. Roggenbuck, MS, CGC (Ohio State University) The institution of Ms. Roggenbuck has received research support from Packard Foundation.
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Jonathan D. Glass, MD (Emory University School of Medicine) Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apic Bio. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for CIRM. Dr. Glass has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Bryan Cave Leighton Paisner. The institution of Dr. Glass has received research support from NIH. The institution of Dr. Glass has received research support from ALS Assoiciation. The institution of Dr. Glass has received research support from Muscular Dystrophy Assoication.