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Amyotrophic Lateral Sclerosis / Motor Neuron Disease via the FUS Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
6927 FUS 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
6927FUS81406 81406,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by a selective loss of motor neurons in the motor cortex, brain steam, and spinal cord (Tandan, R. and Bradley, W.G. Ann Neurol 18(3):271-280, 1985). The dysfunction and loss of these neurons results in rapid progressive muscle weakness, atrophy and ultimately paralysis of limb, bulbar and respiratory muscles. The mean age of onset of symptoms is about 55 years of age; most cases begin between 40 and 70 years of age. The annual incidence of ALS is 1-2 per 100,000 (Cleveland, D.W. and Rothstein, J.D. Nat Rev Neurosci 2(11):806-819, 2001). The most common symptoms include twitching and cramping of muscles of the hands and feet, loss of motor control in the hands and arms, weakness and fatigue, tripping and falling. Symptoms usually begin with asymmetric involvement of the muscles. As the disease progresses, symptoms may include difficulty in talking, breathing and swallowing, shortness of breath, and paralysis. Cognitive impairment has not been initially associated with ALS. However, frontotemporal dementia (FTD) has been reported in several cases. Dementia has been documented in patients with ALS from different ethnic groups and affects both males and females (Wikström, J. et al. Arch Neurol 39(11):681-683, 1982; Lipton, A.M. et al. Acta Neuropathol 108(5):379-385, 2004; Mitsuyama, Y. and Inoue, T. Neuropathology 29(6):649-654, 2009).

Genetics

About 10% of ALS cases are familial (Emery, A.E. and Holloway, S. Adv Neurol 36:139-147, 1982). In most of these families, ALS is inherited in an autosomal dominant manner (AD-ALS) and is age-dependent with high penetrance. In rare families, the disease is transmitted in an autosomal recessive or dominant X-linked pattern. About 90% of patients with ALS are sporadic cases (SALS) with no known affected relatives. It is unclear how many of the apparently sporadic cases are inherited with low penetrance. The clinical presentations of familial ALS (FALS) and sporadic ALS (SALS) are similar. However, the onset of symptoms in FALS is usually earlier compared to that of SALS (Kinsley and Siddique. GeneReviews, 2012). Autosomal Dominant ALS (AD-ALS) is a clinically and genetically heterogeneous disorder that affects all ethnic groups. At least twelve genetic loci have been reported. Several genes have been identified and include C9orf72, SOD1, FUS, TARDBP, ANG and OPTN. Pathogenic variants in the FUS gene have been reported in patients with ALS (Kwiatkowski, T.J., Jr. et al. Science 323(5918):1205-1208, 2009; Vance, C. et al. Science 323(5918):1208-1211, 2009), and account for up to 4% of AD-ALS cases and 2% of SALS (Hewitt, C. et al. Arch Neurol 67(4):455-61, 2010). About 70 different FUS pathogenic variants have been reported to date. Although most variants are missense resulting in amino acid substitutions, splicing and nonsense variants, as well as small deletions and insertions have been reported. The latter include both frame-shift and in-frame mutations. To date, no pathogenic regulatory variants or large deletions in the FUS gene were reported to be the cause of ALS. All FUS causative variants were heterozygous, except for the H517Q variant, which was found in the homozygous state in four patients from a consanguineous family of Cape Verdean origin (Kwiatkowski, T.J., Jr. et al, 2009). The FUS gene encodes the FUS (fused in sarcoma) protein, which has been involved in several cellular processes including transcription regulation and alternative splicing.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test allows the detection of mutations in up to 4% of AD-ALS cases and 2% of SALS (Hewitt, C. et al. Arch Neurol 67(4):455-461, 2010).

Thus far, no pathogenic gross deletions or duplications have been reported in the FUS gene (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the FUS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with symptoms suggestive of ALS or Motor Neuron Disease with or without FTD, and no C9orf72-GGGGCC repeat expansion or mutations in the SOD1 gene. Patients with AR-ALS of Cape Verdean origin are also candidates.

Gene

Official Gene Symbol OMIM ID
FUS 137070
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Amyotrophic Lateral Sclerosis Type 6 608030

Citations

  • Cleveland, D.W. and Rothstein, J.D. (2001). "From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS." Nat Rev Neurosci 2(11): 806-819. PubMed ID: 11715057
  • Emery A.E., Holloway S. 1982. Advances in Neurology. 36: 139-47. PubMed ID: 7180680
  • Hewitt, C. et al (2010). "Novel FUS/TLS mutations and pathology in familial and sporadic amyotrophic lateral sclerosis."  Arch Neurol 67(4):455-61. PubMed ID: 20385912
  • Human Gene Mutation Database (Bio-base).
  • Kinsley L, Siddique T. 2015 Amyotrophic Lateral Sclerosis Overview. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301623
  • Kwiatkowski, T. J., Jr., et.al. (2009). "Mutations in the FUS/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis." Science 323(5918): 1205-1208. PubMed ID: 19251627
  • Lipton, A.M. et al. (2004). "Frontotemporal lobar degeneration with motor neuron disease-type inclusions predominates in 76 cases of frontotemporal degeneration". Acta Neuropathol 108(5):379-385. PubMed ID: 15351890
  • Mitsuyama, Y. and Inoue, T. (2009). "Clinical entity of frontotemporal dementia with motor neuron disease". Neuropathology 29(6):649-654. PubMed ID: 19780984
  • Tandan, R. and Bradley, WG. (1985). "Amyotrophic lateral sclerosis: Part 1. Clinical features, pathology, and ethical issues in management." Ann Neurol 18(3): 271-280. PubMed ID: 4051456
  • Vance, C., et.al. (2009). "Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6." Science 323(5918): 1208-1211. PubMed ID: 19251628
  • Wikström, J. et al. (1982). "Classic amyotrophic lateral sclerosis with dementia". Arch Neurol 39(11):681-683. PubMed ID: 7125994

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
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