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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 5247 | KIF5A | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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.
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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ORDER OPTIONS
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