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Sodium Channel, Voltage-Gated, Type IX, Alpha Subunit Disorders via the SCN9A 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
3067 SCN9A 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3067SCN9A81479 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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Small fiber neuropathy (OMIM 133020) is a relatively common adult onset disorder characterized by burning, neuropathic pain and autonomic symptoms of orthostatic dizziness, palpitations, dry eyes, and dry mouth (Faber et al. Ann Neurol 71:26-39, 2012). Nerve biopsies of affected individuals show that the intraepidermal density of small diameter nerve fibers is reduced. A minority of the eight Dutch patients reported by Faber et al. reported significant gastrointestinal symptoms while most of this cohort experienced persistence of the pain or burning over several years to involve the hands, mouth, or body.

Primary erythermalgia (OMIM 133020) is characterized by neuropathic pain of the feet and lower legs described by patients as a moderate to severe burning sensation. Affected areas feel warm and appear red and swollen. Symptoms are provoked by exercise, standing, and exposure to heat and humidity (Michiels et al. Arch Neurol 62:1587-1590, 2005). Onset can occur anywhere from childhood to adulthood. The frequency and severity of episodes increase with age. Variable levels of pain relief may be achieved by cooling affected areas and use of pain medications (Herskovitz et al. Neurology 43:621-622, 1993).

Familial febrile seizures, type 3B (OMIM 613863) and generalized epilepsy with febrile seizures-plus, type 7 (OMIM 613863, GEFS+, type 7) are related disorders of childhood-onset febrile seizures. Whereas familial febrile seizures, type 3B resolves in early childhood, the GEFS+, type 7 phenotype progresses to febrile and afebrile seizures and, in some patients, epilepsy (Singh et al. PLoS Genet 5:e1000649, 2009; Singh et al. Ann Neurol 45: 75-81, 1999).

Paroxysmal extreme pain disorder (OMIM 167400) is characterized by pain and autonomic dysfunction (Fertleman et al. Neuron 52:767-774, 2006). Four types of stimuli cause painful episodes in affected individuals: 1) the birth process induces pain crisis as evidenced by red and stiff affected newborns; 2) defecation in infants and young children triggers rectal pain; 3) provoked or, more commonly lack of a stimulus, leads to ocular pain; 4) yawning or eating triggers mandibular pain. This disorder is distinct in that pain, which is extreme, is restricted to the rectal, ocular, and mandibular areas. Skin flushing, syncope, excess secretions from the eyes and nose are presenting autonomic symptoms. Episodes of pain in this disorder may decrease with age, however they do not resolve completely.

Channelopathy-associated insensitivity to pain (OMIM 243000) is characterized by congenital inability to perceive any form of pain, but with normal sensory perception of touch, pressure, tickle, and temperature (Cox et al. Nature 444:894-898, 2006). The first molecularly confirmed cases were from Northern Pakistan, however, confirmed cases from many different nationalities have subsequently been reported (Goldberg et al. Clin Genet 71: 311-319, 2007). In one study, patients were found to also lack the ability to smell (Weiss et al. Nature 472: 186-190, 2011).

Genetics

Heterozygous gain-of-function missense mutations in SCN9A cause primary erythermalgia, small fiber neuropathy, familial febrile seizures, type 3B, generalized epilepsy with febrile seizures-plus, type 7, and paroxysmal extreme pain disorder. Channelopathy-associated insensitivity to pain is inherited as an autosomal recessive disorder. All mutations reported to date in this recessive disorder result in loss of function via premature stop codons or frame-shifts and protein truncations.

Clinical Sensitivity - Sequencing with CNV PG-Select

Analytical sensitivity may be high because all SCN9A mutations reported to date are expected to be detected by direct sequencing of genomic DNA. Clinical sensitivity is problematic to predict due to genetic heterogeneity of these disorders and the dearth of documented cases.

Testing Strategy

This test provides full coverage of all coding exons of the SCN9A gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical features of one of the SCN9A-related disorders. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SCN9A.

Gene

Official Gene Symbol OMIM ID
SCN9A 603415
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Episodic Pain Syndrome Panel
Hereditary Sensory and Autonomic Neuropathy Panel

Citations

  • Cox, J. J. et al. (2006).   PubMed ID: 17167479
  • Faber, C. G. et al. (2012). PubMed ID: 21698661
  • Fertleman CR et al. (2006). PubMed ID: 17145499
  • Goldberg, Y. P. et al. (2007). PubMed ID: 17470132
  • Herskovitz, S. et al. (1993). PubMed ID: 8451013
  • Michiels, J. J. et al. (2005).   PubMed ID: 16216943
  • Singh N.A. et al. 2009. Plos Genetics. 5: e1000649. PubMed ID: 19763161
  • Singh R. et al. 1999. Annals of Neurology. 45: 75-81. PubMed ID: 9894880
  • Weiss, J. et al. (2011). PubMed ID: 21441906

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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