DNA icon

Spastic Paraplegia 3A via the ATL1 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
15227 ATL1 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15227ATL181406 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

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Spastic paraplegia 3A (SPG3A) is a type of hereditary spastic paraplegia (HSP) characterized by progressive bilateral spasticity and weakness of lower limbs, and diminished vibration sensation. Over 80% of affected individuals manifest spastic gait before the age of 10 years and the rate of progression is slow. The average onset age is 4 years (Hedera 2010). In general, penetrance is high (80%-90%) in SPG3A patients and is not age-dependent (Durr et al. 2004). Typically, SPG3A with early-onset is characterized by a pure HSP phenotype, i.e., the symptoms are limited to lower limbs. However, complicated cases with others symptoms such as axonal motor neuropathy and distal amyotrophy, cerebellar ataxia and intellectual disability have also been reported (Scarano et al. 2005; Haberlová et al. 2008; Fusco et al. 2012).

Similar to other types of HSP, the genotype-phenotype correlation of SPG3A is not clear; therefore the diagnosis of SPG3A can be established only via molecular genetic testing.

Genetics

SPG3A is caused by pathogenic variants in the ATL1 gene (Zhao et al. 2001). ATL1 is the only known causative gene for this type of HSP. SPG3A accounts for almost 7% of familial HSP, approximately 3.5% of sporadic HSP, and 10%-15% of autosomal dominant (AD) HSP (Lo Giudice et al. 2014; Fink et al. 1996). It is the most prevalent type of early-onset cases, accounting for approximately 40% of AD-HSP with onset before the age of 10 years (Abel et al. 2004; Durr et al. 2004). Although SPG3A is typically inherited in an AD manner, an extremely unusual recessive case has been reported (Khan et al. 2014).

ATL1 encodes protein atlastin-1, a member of the dynamin family predominantly expressed in the pyramidal neurons. ATL1 plays important roles in neurite outgrowth, intracellular membrane trafficking, and in the formation of the tubular ER network (Rismanchi et al. 2008; Hu et al. 2009). The protein contains two transmembrane domains and a GTP binding domain (Zhu et al. 2003). Most SPG3A-causing variants are missense variants in the GTPase binding domain, resulting in decreased catalytic activity (Hedera 2010).

SPG3A is allelic with another autosomal dominant disorder, hereditary sensory neuropathy type 1 (HSN1). Pathogenic variants in ATL1 have been identified in HSN1 patients (Guelly et al. 2011; Leonardis et al. 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect pathogenic variants in ATL1 in approximately 7% of familial, and 3.5% of sporadic or apparent sporadic hereditary spastic paraplegia (HSP) patients (Lo Giudice et al. 2014). For autosomal dominant HSP, approximately 10%-15% of all patients and 40% of patients with early onset (< 10 years) will be found to have a pathogenic variant in ATL1 (Fink et al. 1996; Durr et al. 2004).

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 ATL1 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

Individuals with symptoms consistent with autosomal dominant HSP (particularly the ones with early-onset), and family members of patients who have known ATL1-HSP mutations are ideal candidates for this test.

Gene

Official Gene Symbol OMIM ID
ATL1 606439
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 3 AD 182600

Citations

  • Abel A. et al. 2004. Neurogenetics. 5: 239-43. PubMed ID: 15517445
  • Dürr A. et al. 2004. Archives of Neurology. 61: 1867-72. PubMed ID: 15596607
  • Fink J.K. et al. 1996. Neurology. 46: 1507-14. PubMed ID: 8649538
  • Fusco C. et al. 2012. Journal of Child Neurology. 27: 1348-50. PubMed ID: 22378671
  • Guelly C. et al. 2011. American Journal of Human Genetics. 88: 99-105. PubMed ID: 21194679 PubMed ID: 21194679
  • Haberlová J. et al. 2008. Journal of Neurology. 255: 927-8. PubMed ID: 18446315
  • Hedera P. 2010. Spastic Paraplegia 3A. 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: 20862796
  • Hu J. et al. 2009. Cell. 138: 549-61. PubMed ID: 19665976
  • Khan T.N. et al. 2014. European Journal of Human Genetics : Ejhg. 22: 1180-4. PubMed ID: 24473461
  • Leonardis L. et al. 2012. European Journal of Neurology. 19: 992-8. PubMed ID: 22340599
  • Lo Giudice T. et al. 2014. Experimental Neurology. 261: 518-39. PubMed ID: 24954637
  • Rismanchi N. et al. 2008. Human Molecular Genetics. 17: 1591-604. PubMed ID: 18270207
  • Scarano V. et al. 2005. Journal of Neurology. 252: 901-3. PubMed ID: 15742100
  • Zhao X. et al. 2001. Nature Genetics. 29: 326-31. PubMed ID: 11685207
  • Zhu P.P. et al. 2003. The Journal of Biological Chemistry. 278: 49063-71. PubMed ID: 14506257

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
×