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Childhood Absence Epilepsy and Epileptic Encephalopathy via the GABRB3 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
4157 GABRB3 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4157GABRB381479 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

  • Eric Bend, PhD

Clinical Features and Genetics

Clinical Features

Childhood Absence Epilepsy (CAE) is a neurological condition defined by onset of absence seizures between ages 2 and 12 years in otherwise developmentally normal children. Absence seizures present as staring episodes often with eyelid myoclonia and can be triggered by light. Seizures are brief, lasting 3-20 seconds, and frequent, occurring in excess of 10 seizures per day (Tanaka et al. 2008). Seizures remit at the end of childhood, between 10 and 18 years of age. EEG recordings reveal generalized high amplitude spike and slow wave complexes. CAE is not progressive, is not associated with myoclonic jerks and does not affect intellect.

Lennox-Gastaut syndrome (LGS) is a type of childhood epileptic encephalopathy. Epilepsy onset occurs at around 2 years of age. LGS patients suffer from multiple seizure types including tonic, atonic, absence and myoclonic seizures. EEG recordings reveal generalized slow spike and slow wave (>2.5Hz) activity (Khan and Al Baradie 2012). LGS patients have mild to moderate intellectual disability.

Infantile spasms (IS) or West syndrome is a seizure disorder with onset in the first year of life. The three key clinical features of IS are: infantile spasms, developmental delay and hypsarrhythmia on EEG (Khan and Al Baradie 2012). Underlying structural brain abnormalities explain ~90% of all IS and LGS cases (Depienne et al. 2012).

Genetics

CAE is inherited in an autosomal dominant manner and can be caused by missense mutations in the GABRB3 gene (Tanaka et al. 2008). De novo missense mutations in the GABRB3 gene were also identified in patients with IS and LGS (Allen et al. 2013).

The GABRB3 gene encodes the B3 subunit of the neuronally expressed, pentameric GABAA receptor. GABA is an inhibitory neurotransmitter responsible for modulating signaling in the brain. Mutations in GABAA receptor subunits decrease the receptor's response to GABA, thus reducing GABA-signaling. It is proposed that this loss of inhibition in neurons results in increased synaptic excitation and epilepsy (Lachance-Touchette et al. 2011). B3 subunits are present in most GABAA receptors during early childhood, and B3 subunits are gradually replaced by B2 subunits with age (Gurba et al. 2012). This early developmental role for B3 subunits might explain why disruption of GABRB3 results in childhood epilepsies.

Clinical Sensitivity - Sequencing with CNV PG-Select

Likely pathogenic de novo variants in GABRB3 were identified in ~1.5% (4 of 264) of patients with diagnoses of infantile spasms or Lennox-Gastaut syndrome (Allen et al. 2013).

Testing Strategy

This test provides full coverage of all coding exons of the GABRB3 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

GABRB3 testing should be considered for patients with childhood absence epilepsy in which family history is consistent with autosomal dominant inheritance or patients with LGS or IS of unknown cause.

Gene

Official Gene Symbol OMIM ID
GABRB3 137192
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epilepsy, Childhood Absence 5 612269

Citations

  • Allen AS, Berkovic SF, Cossette P, Delanty N, Dlugos D, Eichler EE, Epstein MP, Glauser T, Goldstein DB, Han Y, Heinzen EL, Hitomi Y, Howell KB, Johnson MR, Kuzniecky R, Lowenstein DH, Lu YF, Madou MR, Marson AG, Mefford HC, Esmaeeli Nieh S, O'Brien TJ, Ottman R, Petrovski S, Poduri A, Ruzzo EK, Scheffer IE, Sherr EH, Yuskaitis CJ, Abou-Khalil B, Alldredge BK, Bautista JF, Berkovic SF, Boro A, Cascino GD, Consalvo D, Crumrine P, Devinsky O, Dlugos D, Epstein MP, Fiol M, Fountain NB, French J, Friedman D, Geller EB, Glauser T, Glynn S, Haut SR, Hayward J, Helmers SL, Joshi S, Kanner A, Kirsch HE, Knowlton RC, Kossoff EH, Kuperman R, Kuzniecky R, Lowenstein DH, McGuire SM, Motika PV, Novotny EJ, Ottman R, Paolicchi JM, Parent JM, Park K, Poduri A, Scheffer IE, Shellhaas RA, Sherr EH, Shih JJ, Singh R, Sirven J, Smith MC, Sullivan J, Lin Thio L, Venkat A, Vining EP, Von Allmen GK, Weisenberg JL, Widdess-Walsh P, Winawer MR. 2013. De novo mutations in epileptic encephalopathies. Nature 501: 217–221. PubMed ID: 23934111
  • Depienne C, Gourfinkel-An I, Baulac S, LeGuern E. 2012. Genes in infantile epileptic encephalopathies. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, and Delgado-Escueta AV, editors. Jasper’s Basic Mechanisms of the Epilepsies, 4the. Bethesda (MD): National Center for Biotechnology Information (US),. PubMed ID: 22787626
  • Gurba KN, Hernandez CC, Hu N, Macdonald RL. 2012. GABRB3 Mutation, G32R, Associated with Childhood Absence Epilepsy Alters 1 3 2L -Aminobutyric Acid Type A (GABAA) Receptor Expression and Channel Gating. Journal of Biological Chemistry 287: 12083–12097. PubMed ID: 22303015
  • Khan S, Baradie R Al. 2012. Epileptic Encephalopathies: An Overview. Epilepsy Research and Treatment 2012: 1–8. PubMed ID: 23213494
  • Lachance-Touchette P et al. 2011. The European Journal of Neuroscience. 34: 237-49. PubMed ID: 21714819
  • Tanaka M, Olsen RW, Medina MT, Schwartz E, Alonso ME, Duron RM, Castro-Ortega R, Martinez-Juarez IE, Pascual-Castroviejo I, Machado-Salas J, Silva R, Bailey JN, et al. 2008. Hyperglycosylation and Reduced GABA Currents of Mutated GABRB3 Polypeptide in Remitting Childhood Absence Epilepsy. The American Journal of Human Genetics 82: 1249–1261. PubMed ID: 18514161

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

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1) Select Test Method (Backbone)


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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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