Spastic Paraplegia 11 via the SPG11 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
15299 SPG11 81407 81407,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15299SPG1181407 81407, 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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Spastic paraplegia 11 (SPG11) is a type of hereditary spastic paraplegia (HSP) and is characterized by progressive spasticity and weakness of the lower limbs (Stevanin et al. 2008a). Most SPG11 cases are complex, i.e., the spastic paraparesis are associated with other features, such as cognitive impairments, thin corpus callosum (TCC), white and grey matter abnormalities (Stevanin et al. 2008b; Franca et al. 2012). Onset is typically early (age 1-31 years) and most SPG11 patients become wheelchair users 10-20 years after disease onset (Stevanin et al. 2008a).

Although cognitive impairments and TCC serve as phenotype predictors of SPG11, these features may also be present in other HSP patients with a different genetic basis. In addition, pathogenic variants in SPG11 can also cause Charcot-Marie-Tooth disease type 2X (Montecchiani et al. 2016) and juvenile Amyotrophic Lateral Sclerosis type 5 (ALS5) (Orlacchio et al. 2010), different neurological disorders with overlapping features. Molecular genetic testing is very useful in a precise diagnosis of this type of disease.

Genetics

SPG11 is inherited as an autosomal recessive (AR) disorder and it is known to be the most common type of AR-HSP. SPG11 (also known as KIAA1840) is the only gene in which pathogenic variants cause SPG11 (Stevanin et al. 2007). The SPG11 gene encodes spatacsin (for spasticity with thin or atrophied corpus callosum syndrome protein), a protein expressed throughout the nervous system. The function of spatacsin is not well understood, but a recent study suggests that it may play roles in axonal maintenance and intracellular protein trafficking (Perez-Branguli et al. 2014). To date, with the exception of a few (<10) missense variants reported, all the identified pathogenic variants (>150) in SPG11 are either nonsense or deletions/duplications leading to a frameshift, strongly suggesting a loss-of-function mechanism (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

SPG11 accounts for approximately 21% of all autosomal recessive (AR) hereditary spastic paraplegia (HSP) (Stevanin et al. 2008b). For patients with early-onset and cognitive impairments associated with thin corpus callosum (TCC), pathogenic variants in SPG11 may account for up to 59% of cases (Stevanin et al. 2008b; Denora et al. 2009).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the SPG11 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients showing features consistent with AR-HSP and family members of patients who have known SPG11-HSP mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SPG11.

Gene

Official Gene Symbol OMIM ID
SPG11 610844
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 11 AR 604360

Citations

  • Denora P.S. et al. 2009. Human Mutation. 30: E500-19. PubMed ID: 19105190
  • França M.C. Jr. et al. 2012. Journal of Neurology, Neurosurgery, and Psychiatry. 83: 828-33. PubMed ID: 22696581
  • Human Gene Mutation Database (HGMD).
  • Montecchiani C. et al. 2016. Brain : a Journal of Neurology. 139: 73-85. PubMed ID: 26556829
  • Orlacchio A. et al. 2010. Brain : a Journal of Neurology. 133: 591-8. PubMed ID: 20110243
  • Pérez-Brangulí F. et al. 2014. Human Molecular Genetics. 23: 4859-74. PubMed ID: 24794856
  • Stevanin G et al. 2008a. Spastic Paraplegic 11. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301389
  • Stevanin G. et al. 2007. Nature Genetics. 39: 366-72. PubMed ID: 17322883
  • Stevanin G. et al. 2008b. Brain : a Journal of Neurology. 131: 772-84. PubMed ID: 18079167

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.

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 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.

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