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Spastic Paraplegia 6 via the NIPA1 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
8801 NIPA1 81404 81404,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8801NIPA181404 81404,81479 $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 6 (SPG6) is a type of hereditary spastic paraplegia (HSP) characterized by a severe and progressive spasticity and weakness of the lower limbs (Lo Giudice et al. 2014). Typically, SPG6 exhibits a pure HSP phenotype, i.e., the symptoms are limited to the lower limbs. However, rare cases “complicated” with peripheral neuropathy, cognitive impairment or epilepsy have also been reported (Klebe et al. 2007; Du et al. 2011; Svenstrup et al. 2011). Onset in late teenage or early adulthood is common, but with a range from 8 to 40 years (Denora et al. 2013). SPG6 typically presents with relatively aggressive progression, leading to wheelchair dependency in most patients (Botzolakis et al. 2011).

Genetics

SPG6 is inherited in an autosomal dominant (AD) manner and is caused by pathogenic variants at the 15q11.2 locus of the NIPA1 (non-imprinted in Prader-Willi/Angelman syndrome region protein 1) gene (Rainier et al. 2003). NIPA1 gene encodes a potential Mg2+ transporter, which is highly expressed in the nervous system. NIPA1 protein localizes to plasma membrane, endosomes and Golgi apparatus (Rainier et al. 2003; Goytain et al. 2007). NIPA1 is an inhibitor of BMP (bone morphogenic protein) signaling (Tsang et al. 2009), which is very important for distal axonal function (Zhong et al. 2014). To date, at least 4 different causative variants (c.134C>G, c.298G>A, c.316G>C and c.316G>A) have been reported in SPG6 patients and all of them are missense (Human Gene Mutation Database). c.316 might be a mutational hot spot in the NIPA1 gene, and studies from unrelated families have proved c.316G>A as a recurrent de novo mutation (Hedera et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

It is difficult to estimate the clinical sensitivity of this test due to the lack of large cohort studies. In a study of 110 Caucasian autosomal dominant HSP families who are negative for SPG4 (spast), SPG6 accounts for <1% (1/110) patients (Klebe et al. 2007).

Testing Strategy

This test provides full coverage of all coding exons of the NIPA1 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

Candidates for this test are patients manifesting features consistent with autosomal dominant HSP and family members of patients who have known NIPA1-HSP mutations.

Gene

Official Gene Symbol OMIM ID
NIPA1 608145
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Spastic Paraplegia 6 AD 600363

Citations

  • Botzolakis E.J. et al. 2011. Molecular and Cellular Neurosciences. 46: 122-35. PubMed ID: 20816793
  • Denora P.S. et al. 2013. Handbook of Clinical Neurology. 113: 1899-912. PubMed ID: 23622413
  • Du J. et al. 2011. Clinical Neurology and Neurosurgery. 113: 480-2. PubMed ID: 21419568
  • Goytain A. et al. 2007. The Journal of Biological Chemistry. 282: 8060-8. PubMed ID: 17166836
  • Hedera P. 2013. Journal of the Neurological Sciences. 335: 231-2. PubMed ID: 24075313
  • Human Gene Mutation Database (Bio-base).
  • Klebe S. et al. 2007. Neurogenetics. 8: 155-7. PubMed ID: 17205300
  • Lo Giudice T. et al. 2014. Experimental Neurology. 261: 518-39. PubMed ID: 24954637
  • Rainier S. et al. 2003. American Journal of Human Genetics. 73: 967-71. PubMed ID: 14508710
  • Svenstrup K. et al. 2011. European Journal of Neurology. 18: 1197-9. PubMed ID: 21599812
  • Tsang H.T. et al. 2009. Human Molecular Genetics. 18: 3805-21. PubMed ID: 19620182
  • Zhong J., Zou H. 2014. Current Opinion in Neurobiology. 27: 127-34. PubMed ID: 24713578

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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