• Test Code:
    1010
  • Department:
  • Test Synonyms:
    ALSALS2ANGATXN2C9ORF72CHMP2BDCTN1FIG4FUSNEFHOPTN PFN1PRPH2SETXSIGMAR1SOD1SPG20TARDBPUBQLN2VAPBVCPVEGFA
  • CPT Code(s):
    81406
Background:

Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, invariably fatal, neurodegenerative disease that affects nerve cells in the brain and the spinal cord. More than 12,000 people in the U.S. have a definite diagnosis of ALS, for a prevalence of 3.9 cases per 100,000 persons in the U.S. general population, according to a report on data from the National ALS Registry. There are two different types of ALS, sporadic (90-95% of all cases) and familial (5-10% of all cases) in the U.S.

Familial ALS means the disease is inherited. In those families, there is a 50% chance each offspring will inherit the gene mutation and may develop the disease. The familial form of ALS is Mutations in more than a dozen genes have been found to cause familial ALS. ALS can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner.

*Approximately 40% of familial ALS cases (and a small percentage of sporadic cases) result from a hexanucleotide repeat GGGGCC in the C9orf72 gene. This panel does NOT include C9orf72 hexanucleotide repeat expansion analysis.

Reasons for Referral:

  • Genetic etiology of suspension of ALS
  • Genetic diagnosis of ALS with clinical symptoms including muscle weakness, dysarthria
  • Positive family history
  • Carrier testing

Methodology:

Next generation sequencing will analyze the exons or coding regions of 21 Amyotrophic Lateral Sclerosis -associated genes using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions.  Promoter, intronic, etc. regions are not assessed on our assay, but may contain variants that impact gene function.

Amyotrophic Lateral Sclerosis Panel (21 genes): ALS2, ANG, ATXN2, C9ORF72*, CHMP2B, DCTN1, FIG4, FUS, NEFH, OPTN, PFN1, PRPH2, SETX, SIGMAR1, SOD1, SPG20, TARDBP, UBQLN2, VAPB, VCP, VEGFA

*C9orf72 hexanucleotide repeat expansion not performed

Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)

Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks

DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. ALS Fact Sheet
  2. acoangeli A, Al Khleifat A, Jones AR, et al. C9orf72 intermediate expansions of 24-30 repeats are associated with ALS. Acta Neuropathol Commun. 2019;7(1):115. Published 2019 Jul 17. doi:10.1186/s40478-019-0724-4
  3. Mehta, P, Antao V, Kaye W, et al. Prevalence of Amyotrophic Lateral Sclerosis - United States, 2010–2011. Retrieved from Prevalence of Amyotrophic Lateral Sclerosis — United States, 2010–2011
  4. Siddique N, Siddique T. Amyotrophic Lateral Sclerosis Overview. 2001 Mar 23 [Updated 2019 Oct 3]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: Amyotrophic Lateral Sclerosis Overview 

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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