Juvenile Myoclonic Epilepsy via the GABRA1 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
7123 GABRA1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7123GABRA181479 81479(x2) $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

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Idiopathic generalized epilepsy (IGE, OMIM 600669) is a clinically and genetically heterogeneous group of epilepsy disorders. IGE has a strong genetic basis, is not usually associated with cognitive defects and presents during childhood or adolescence. Sub-types of IGE include: juvenile myoclonic epilepsy (JME), childhood absence epilepsy (CAE) and generalized epilepsy with febrile seizures plus (GEFS+).

JME (OMIM 611136) is further subdivided into two subsyndromes. Classic JME presents during teenage years as myoclonic seizures and ultimately progresses to grand mal seizures. Notably, absence seizures are not seen in classic JME cases or family members (Delgado-Escueta. Curr Rev Clin Sci 7(3):61-67, 2007). In JME with adolescent absence, patients present with myoclonic seizures and grand mal convulsions, but patients and family members may also experience absence seizures. In both forms of JME, EEGs display diffuse 3.5-6 Hz polyspike and slow wave complexes, even if patients are clinically asymptomatic (Medina et al. Neurology 70(22 Pt 2):2137-2144, 2008).

Genetics

JME is inherited in an autosomal dominant manner. The majority of reported variants in GABRA1 are single nucleotide substitutions or small deletions that would be detectable by sequencing. Heterozygous mutations in the gene GABRA1 have been reported in multiple French-Canadian families with JME (Cossette et al. Nat Genet 31(2):184-189, 200; Lachance-Touchette et al. Eur J Neurosci 34(2):237-249, 2011).

GABRA1 encodes a transmembrane subunit of the GABAA receptor. GABAA receptors mediate fast synaptic inhibition in the brain. Mutations in GABRA1 reduce GABA-activated currents in vitro (Cossette et al., 2002; Gallagher et al. J Neurosci. 24(24):5570-5578, 2004). Disruption of inhibitory GABAA signaling may increase the number of excitatory synapses in the brain and lead to epilepsy. Multiple GABAA receptor subunits have been implicated in various types of IGE (Macdonald et al. J Physiol. 588(Pt 11):1861-1869, 2010).

Clinical Sensitivity - Sequencing with CNV PG-Select

One study found GABRA1 mutations in ~2% of patients diagnosed with IGE (Lachance-Touchette et al. Eur J Neurosci 34(2):237-249, 2011).

Testing Strategy

This test provides full coverage of all coding exons of the GABRA1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for GABRA1 testing include patients with symptoms of JME.

Gene

Official Gene Symbol OMIM ID
GABRA1 137160
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epilepsy, Juvenile Myoclonic 5 611136

Citations

  • Cossette, P. et al. (2002). "Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy." Nat Genet 31(2):184-189. PubMed ID: 11992121
  • Delgado-Escueta, A. V. (2007). "Advances in Genetics of Juvenile Myoclonic Epilepsies." Curr Rev in Clin Sci 7(3):61-67. PubMed ID: 17520076
  • Gallagher, M. J. et al. (2004). "The juvenile myoclonic epilepsy GABAA receptor α1 subunit mutation A322D produces asymmetrical, subunit position-dependent reduction of heterozygous receptor currents and α1 subunit protein expression." J Neurosci  24(24):5570-5578. PubMed ID: 15201329
  • Lachance-Touchette P et al. 2011. The European Journal of Neuroscience. 34: 237-49. PubMed ID: 21714819
  • Macdonald, R.L. et al. (2010). "Mutations in GABAA receptor subunits associated with genetic epilepsies." J Physiol 588(Pt 11):1861-1869. PubMed ID: 20308251
  • Medina, M.T. et al. (2008). "Novel mutaitons in Myoclonin1/EFHC1 in sporadic and familial juvenile myoclonic epilepsy."  Neurology 70(22 Pt 2): 2137-2144. PubMed ID: 18505993

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.
Total Price: $
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