Autosomal Recessive Spinocerebellar Ataxia and Amyotrophic Lateral Sclerosis Type 4 via the SETX Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes
3227 SETX$640 8140681406,81479 Add to Order

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.

Targeted Testing

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

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Autosomal Recessive Cerebellar Ataxias (ARCAs) are a heterogeneous group of neurological disorders involving both the central and peripheral nervous systems, and in some cases additional systems and organs (Palau and Espinós Orphanet J Rare Dis 1:47, 2006). ARCAs involve a wide range of clinical features including gait imbalance, diminished tendon reflexes, involuntary movements and ophthalmological and cutaneous abnormalities. ARCAs are distinguished from other cerebellar ataxias by an autosomal recessive inheritance, onset before the age of 20 years and slow progression (Fogel and Perlman Lancet Neurol 6:245-257, 2007).

Amyotrophic Lateral Sclerosis Type 4 (ALS4, OMIM 602433) is a neurological disease characterized by juvenile onset, usually before the age of 25 years, a slow progression and a normal life span. Typical symptoms include distal muscle weakness and atrophy, brisk deep-tendon reflexes and a positive Babinski sign (Chen et al. Am J Hum Genet 74:1128-1135, 2004).

Genetics

Mutations in the SETX gene cause one form of ARCAs: Spinocerebellar Ataxia, Autosomal Recessive 1 (SCAR1, OMIM 606002). Because oculomotor apraxia was observed in the initial patients with SETX mutations, this form of the disease was also referred to as Ataxia-Oculomotor Apraxia 2 (Moreira et al. Nat Genet 36:225-227, 2004). Subsequent reports detected oculomotor apraxia in only 50% of patients with SETX mutations (Moreira and Koenig, GeneReveiws, 2007). SCAR1 patients constitute a heterogeneous group presenting with cerebellar ataxia and a range of additional features, including oculomotor apraxia, elevated serum levels of α-fetoprotein and creatine kinase (Moreira et al. Nat Genet 36:225-227, 2004), distal amyotrophy, peripheral neuropathy (Duquette et al. Ann Neurol 57:408-414, 2005; Asaka et al. Neurology 66:1580-1581, 2006) and nystagmus, spasticity and areflexia (Nicolaou et al. BMC Med Genet 9:28, 2008). At least 27 SETX mutations have been reported in patients with SCAR1. These mutations are distributed throughout the gene and include missense, nonsense, splicing and small deletions/insertions.

In addition to the SCAR1-causative mutations, three dominant missense mutations in the SETX gene were identified in patients with ALS4 (Chen et al. Am J Hum Genet 74:1128-1135, 2004) and one dominant missense mutation was found in a Chinese patient with apparently isolated ALS (Zhao et al. Amyotroph Lateral Scler 10:118-122, 2009).

Testing Strategy

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

Clinical Sensitivity - Sequencing and CNV

Currently unknown.

Indications for Test

Patients with SCAR1 (OMIM 606002) and patients with ALS 4 (OMIM 602433). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SETX.

Gene

Official Gene Symbol OMIM ID
SETX 608465
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Panel
Ataxia with Oculomotor Apraxia Panel
Distal Hereditary Motor Neuropathy Panel

Citations

  • Asaka, T., et.al. (2006). "Autosomal recessive ataxia with peripheral neuropathy and elevated AFP: novel mutations in SETX." Neurology 66(10): 1580-1. PubMed ID: 16717225
  • Chen, Y. Z., et.al. (2004). "DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4)." Am J Hum Genet 74(6): 1128-35. PubMed ID: 15106121
  • Duquette, A., et.al. (2005). "Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy." Ann Neurol 57(3): 408-14. PubMed ID: 15732101
  • Fogel, B. L., Perlman, S. (2007). "Clinical features and molecular genetics of autosomal recessive cerebellar ataxias." Lancet Neurol 6(3): 245-57. PubMed ID: 17303531
  • Maria-Céu Moreira, Michel Koenig (2009). "Ataxia with Oculomotor Apraxia Type 2." GeneReviews. PubMed ID: 20301333
  • Moreira M.C. et al. 2004. Nature Genetics. 36: 225-7. PubMed ID: 14770181
  • Nicolaou, P., et.al. (2008). "A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia." BMC Med Genet 9: 28. PubMed ID: 18405395
  • Palau, F., Espinos, C. (2006). "Autosomal recessive cerebellar ataxias." Orphanet J Rare Dis 1: 47. PubMed ID: 17112370
  • Zhao, Z. H., et.al. (2009). "A novel mutation in the senataxin gene identified in a Chinese patient with sporadic amyotrophic lateral sclerosis." Amyotroph Lateral Scler 10(2): 118-22. PubMed ID: 19058054

Ordering/Specimens

Ordering Options

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.

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.

Specimen Types

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