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Spastic Paraplegia 4 via the SPAST Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8079 SPAST 81406 81406,81405 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8079SPAST81406 81406,81405 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Spastic paraplegia 4 (SPG4) is a type of hereditary spastic paraplegia (HSP) characterized by progressive bilateral lower-limb gait spasticity. Over 50% of SPG4 patients have weakness in the legs and abnormal vibration sensation at the ankles. About 30% have sphincter disturbances (Dürr et al. 2003). Onset in young adulthood is common, although in some rare cases symptoms may start as late as in the 70s (Depienne et al. 2007). The average age of onset is 34 (McDermott et al. 2006). SPG4 is the most prevalent type of HSP and accounts for almost 40% of familial HSP and about 18% of sporadic or apparent sporadic HSP (Lo Giudice et al. 2014). Typically, SPG4 is characterized by a pure HSP phenotype, i.e., the symptoms are limited to the lower limbs. A minority of SPG4 cases are complicated by some additional features such as seizures, cerebellar ataxia, and intellectual disability (Nielsen et al. 2004; Ribaï et al. 2008).

Genetics

SPG4 is caused by pathogenic variants in the SPAST gene and hence is also known as SPAST-associated HSP (Hazan et al. 1999). It is inherited in an autosomal dominant manner, though one unusual recessive pathogenic variant has been reported (Lindsey et al. 2000). The penetrance is age dependent, and is estimated to be about 85% by the age of 45 (Fonknechten et al. 2000). A few individuals with a pathogenic variant may remain lifelong asymptomatic (Dürr et al. 1996). In addition, intrafamilial symptomatic variability is considerable, suggesting the involvement of environmental factors and genetic modifiers (Tesson et al. 2015).

SPAST encodes the protein spastin, which is ubiquitously expressed and has a higher expression level in the fetal brain, playing roles in membrane trafficking and microtubule dynamics (Salinas et al. 2007). Spastin has two main domains, the MIT (microtubule interacting and transport) domain, and the AAA (ATPases associated with diverse cellular activities) domain. Over 300 different pathogenic variants have been identified in SPAST gene: nonsense, missense, splice site variants, small indels, and rare large deletions. With rare exceptions, most of the variants are located in the AAA domain, and act by a haploinsufficiency mechanism (Beetz et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in SPAST gene account for almost 40% of hereditary spastic paraplegia (HSP) and about 18% of sporadic or apparent sporadic HSP (Lo Giudice et al. 2014).

Testing Strategy

This test provides full coverage of all coding exons of the SPAST 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Individuals with symptoms consistent with autosomal dominant HSP, and family members of patients who have known SPAST mutations are ideal candidates for this test.

Gene

Official Gene Symbol OMIM ID
SPAST 604277
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 4 AD 182601

Citations

  • Beetz C. et al. 2006. Neurology. 67: 1926-30. PubMed ID: 17035675
  • Depienne C. et al. 2007. Current Opinion in Neurology. 20: 674-80. PubMed ID: 17992088
  • Dürr A. et al. 1996. Brain : a Journal of Neurology. 119 ( Pt 5): 1487-96. PubMed ID: 8931574
  • Dürr et al. 2003. Spastic Paraplegia 4. 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: 20301339
  • Fonknechten N. et al. 2000. Human Molecular Genetics. 9: 637-44. PubMed ID: 10699187
  • Hazan J. et al. 1999. Nature Genetics. 23: 296-303. PubMed ID: 10610178
  • Lindsey JC. et al. 2000. Journal of Medical Genetics. 37: 759-65. PubMed ID: 11015453
  • Lo Giudice T. et al. 2014. Experimental Neurology. 261: 518-39. PubMed ID: 24954637
  • McDermott CJ. et al. 2006. Neurology. 67: 45-51. PubMed ID: 16832076
  • Nielsen JE. et al. 2004. European Journal of Neurology. 11: 817-24. PubMed ID: 15667412
  • Ribaï P. et al. 2008. European Journal of Human Genetics : Ejhg. 16: 97-104. PubMed ID: 17957230
  • Salinas S. et al. 2007. Journal of Neuroscience Research. 85: 2778-82. PubMed ID: 17348041
  • Tesson C. et al. 2015. Human Genetics. 134: 511-38. PubMed ID: 25758904

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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.
Total Price: $
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