Amyotrophic Lateral Sclerosis/Motor Neuron Disease via the TARDBP 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
8829 TARDBP 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8829TARDBP81405 81405(x1), 81479(x1) $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

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.

About 50 different pathogenic TARDBP variants have been reported in patients with ALS with or without FTD (Sreedharan, J. et al. Science 319(5870):1668-1672, 2008; Kabashi, E. et al. Nat Genet 40(5):572-574, 2008; Gitcho, M. A. et al. Ann Neurol 63(4):535-538, 2008; Benajiba, l. et al. Ann Neurol 65(4):470-473, 2009). Except for one single nucleotide duplication, (c.1121dupA, p.Y374*), (Daoud, H. et al. J Med Genet 46(2):112-114, 2009), all variants are of the missense type.

TARDBP mutations account for up to 5% of AD-ALS cases (Wijesekera, L.C. and Leigh, P.N. Orphanet J Rare Dis 4:3, 2009) and 2% of SALS (Daoud, H. et al., 2009).

The TARDBP gene encodes the TAR DNA binding protein (TDP-43), an RNA binding protein that is involved in RNA processing.

Clinical Sensitivity - Sequencing with CNV PG-Select

TARDBP mutations account for up to 5% of AD-ALS cases (Wijesekera and Leigh, P.N. Orphanet J Rare Dis 4:3, 2009) and 2% of SALS (Daoud et al. J Med Genet 46(2):112-114, 2009).

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

Testing Strategy

This test provides full coverage of all coding exons of the TARDBP 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 and FUS genes.

Gene

Official Gene Symbol OMIM ID
TARDBP 605078
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Amyotrophic Lateral Sclerosis Type 10 AD 612069

Related Tests

Name
Amyotrophic Lateral Sclerosis (ALS) via the hnRNPA1 Gene
Amyotrophic Lateral Sclerosis / Motor Neuron Disease via the FUS Gene
Amyotrophic Lateral Sclerosis via the ANG Gene
Amyotrophic Lateral Sclerosis via the OPTN Gene
Amyotrophic Lateral Sclerosis via the UBQLN2 Gene
Amyotrophic Lateral Sclerosis/Motor Neuron Disease via the PFN1 Gene
Autosomal Recessive Spinocerebellar Ataxia and Amyotrophic Lateral Sclerosis Type 4 via the SETX Gene
Spinal Muscular Atrophy, Autosomal Dominant, Adult-Onset and Amyotrophic Lateral Sclerosis-8 via the VAPB Gene

Citations

  • Benajiba L. et al. (2009). TARDBP mutations in motoneuron disease with frontotemporal lobar degeneration. Ann Neurol. 65:470-473. PubMed ID: 19350673
  • Cleveland, D.W. and Rothstein, J.D. (2001). PubMed ID: 11715057
  • Daoud, H. et al. (2009).   PubMed ID: 18931000
  • Emery A.E., Holloway S. 1982. Advances in Neurology. 36: 139-47. PubMed ID: 7180680
  • Gitcho, M. A., et.al. (2008). PubMed ID: 18288693
  • Human Gene Mutation Database (Bio-base).
  • Kabashi, E., et.al. (2008). PubMed ID: 18372902
  • 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
  • Lipton, A.M. et al. (2004).  PubMed ID: 15351890
  • Mitsuyama, Y. and Inoue, T. (2009).  PubMed ID: 19780984
  • Sreedharan, J., et.al. (2008). PubMed ID: 18309045
  • Tandan, R. and Bradley, WG. (1985). PubMed ID: 4051456
  • Wijesekera, L.C. and Leigh, P.N. (2009). PubMed ID: 19192301
  • Wikström, J. et al. (1982). 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

loading Loading... ×

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.
Total Price: $
×
Copy Text to Clipboard
×