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Spastic Paraplegia 10 via the KIF5A 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
5247 KIF5A 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5247KIF5A81479 81479,81479 $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 10 (SPG10) is a type of hereditary spastic paraplegia (HSP) with variable manifestations (Goizet et al. 2009; Crimella et al. 2012). Most patients with this disorder show lower limb hyperreflexia, spasticity and weakness, leading to impaired gait. Upper limb involvement and urinary urgency are frequent, but not always seen. Some patients may also manifest distal sensory impairment (Fichera et al. 2004; Goizet et al. 2009; Crimella et al. 2012). SPG10 has highly variable ages at onset (ranges from 2 to 55 years) and the disease is slowly progressive (Denora et al. 2013; Carosi et al. 2015). SPG10 is very rare with an estimated prevalence < 1/1,000,000 (www.orpha.net).

SPG10 is caused by pathogenic variants in KIF5A gene (Reid et al. 1999; Reid et al. 2002). Rare cases of KIF5A-associated axonal sensorimotor peripheral neuropathy (Crimella et al. 2012; Rinaldi et al. 2015) and neonatal intractable myoclonus (NEIMY) have also been reported (Duis et al. 2016; Rydzanicz et al. 2016).

Genetics

KIF5A-associated SPG10 is inherited in an autosomal dominant (AD) manner. To date, different types of pathogenic variants (missense, nonsense, splicing variants and small deletions) have been found in KIF5A to cause SPG10 (Human Gene Mutation Database). Most of the reported pathogenic variants are located in the highly conserved kinesin motor domain of KIF5A (Ebbing et al. 2008; Rinaldi et al. 2015). KIF5A encodes kinesin heavy chain 5 A, which is involved in anterograde axonal transport (Reid et al. 2002). Functional studies on KIF5A proteins carrying SPG10 pathogenic variants revealed reduced binding on microtubules and reduced transport velocity, indicating that the underlying pathology in this disorder involves altered axonal transport, leading to axonal degeneration (Ebbing et al. 2008; Kawaguchi 2013).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of this test is not certain, due to the lack of large cohort studies. However, previous studies suggest that pathogenic variants in the KIF5A gene may account for 3% of all autosomal dominant Hereditary Spastic Paraplegia (AD HSP) and 10% of complicated AD HSP (Blair et al. 2006; Schule et al. 2008).

No large deletions or duplications involving the KIF5A gene have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the KIF5A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with symptoms consistent with AD HSP may consider this test. The AD HSP patients with peripheral nerve involvement are the best candidates.

Gene

Official Gene Symbol OMIM ID
KIF5A 602821
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Diseases

Name Inheritance OMIM ID
Myoclonus, Intractable, Neonatal AD 617235
Spastic Paraplegia 10 AD 604187

Related Tests

Name
Charcot-Marie-Tooth (CMT) - Axonal Neuropathy Panel
Charcot-Marie-Tooth (CMT) - Comprehensive Panel

Citations

  • Blair M.A. et al. 2006. Neurogenetics. 7: 47-50. PubMed ID: 16489470
  • Carosi L. et al. 2015. Journal of Neurology, Neurosurgery, and Psychiatry. 86: 702-4. PubMed ID: 25352184
  • Crimella C. et al. 2012. Clinical Genetics. 82: 157-64. PubMed ID: 21623771
  • Denora P.S. et al. 2013. Handbook of Clinical Neurology. 113: 1899-912. PubMed ID: 23622413
  • Duis J. et al. 2016. Annals of Neurology. 80: 633-7. PubMed ID: 27463701
  • Ebbing B. et al. 2008. Human Molecular Genetics. 17: 1245-52. PubMed ID: 18203753
  • Fichera M. et al. 2004. Neurology. 63: 1108-10. PubMed ID: 15452312
  • Goizet C. et al. 2009. Human Mutation. 30: E376-85. PubMed ID: 18853458
  • Human Gene Mutation Database (Bio-base).
  • Kawaguchi K. 2013. The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 19: 336-44. PubMed ID: 22785106
  • Reid E. et al. 1999. American Journal of Human Genetics. 65: 757-63. PubMed ID: 10441583
  • Reid E. et al. 2002. American Journal of Human Genetics. 71: 1189-94. PubMed ID: 12355402
  • Rinaldi F. et al. 2015. Journal of Clinical Neuromuscular Disease. 16: 153-8. PubMed ID: 25695920
  • Rydzanicz M. et al. 2016. Clinical Genetics. PubMed ID: 27414745
  • Schüle R. et al. 2008. Journal of Neurology, Neurosurgery, and Psychiatry. 79: 584-7. PubMed ID: 18245137

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

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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.
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