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Developmental and Epileptic Encephalopathy via the GRIN2B 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
7951 GRIN2B 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7951GRIN2B81479 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

GRIN2B-related developmental and epileptic encephalopathy 27 (DEE27) is a rare disorder with an age of onset ranging from infancy to 9 years. Major clinical features (documented in >50% of cases) include severe global developmental delay, severe intellectual disability, and seizures of various types. Minor features of GRIN2B-related disease (<50% of cases) include mild to moderate ID, microcephaly, spasticity, autistic behaviors, and hypotonia. MRI may reveal structural brain malformations in some patients, but the phenotype is highly variable (Platzer et al. 2017. PubMed ID: 28377535).

A diagnosis of DEE27 can provide prognostic and family planning information. This disorder often results in profound disability and reduced life expectancy (Platzer et al. 2017. PubMed ID: 28377535). Treatment typically includes supportive care and management of symptoms. In one individual, dietary supplementation of L-serine was believed to benefit neurological function (Soto et al. 2019. PubMed ID: 31213567).

Genetics

GRIN2B-related developmental and epileptic encephalopathy is autosomal dominant and apparently fully penetrant—to date nearly all cases have involved de novo variants. Nearly all molecular variant types have been associated with GRIN2B-related disease. Pathogenic missense variants are the most frequently reported. They are enriched in the agonist binding domains (S1 and S2) and pore forming transmembrane domains (M1-4). These regions are depleted of natural missense variation in the general population (Karczewski et al. 2020. PubMed ID: 32461654; Swanger et al. 2016. PubMed ID: 27839871; Hu et al. 2016. PubMed ID: 27818011). Pathogenic missense variants have been shown to affect several biophysical properties including, agonist binding, channel gating, and receptor biogenesis. What’s surprising is that variants predicted to result in loss- or gain-of receptor function appear to cause similar neurological phenotypes (Swanger et al. 2016. PubMed ID: 27839871). Predicted null variants (nonsense, frameshifts, and large deletions) are believed to cause disease by haploinsufficiency (Endele et al. 2010. PubMed ID: 20890276; Lemke. 2014. PubMed ID: 24272827; Hu et al. 2016. PubMed ID: 27818011), and GRIN2B is intolerant to chain-terminating variants (Genome Aggregation Database; Karczewski et al. 2020. PubMed ID: 32461654).

GRIN2B(GluN2B)-knockout mice die shortly after birth. Hippocampal neurons in these animals have impaired long term depression, among other phenotypes (Kutsuwada et al. 1996. PubMed ID: 8789948). Therefore, this gene is believed to be essential for the development and function of the mammalian nervous system.

GRIN2B encodes the alpha-2B subunit of N-methyl-D-aspartate NMDA receptors. These ligand-gated ion channels bind glutamate and glycine and serve as important detectors of activity for synaptic plasticity, learning, and memory. NMDA receptors are heterotetrameric, composed of one alpha-1 subunit and one or more alpha-2 A, B, C, or D subunit. This composition is dependent on developmental timing (Endele et al. 2010. PubMed ID: 20890276).

Clinical Sensitivity - Sequencing with CNV PG-Select

The clinical sensitivity of this test alone is expected to be low (<1%).  GRIN2B-related developmental and epileptic encephalopathy is an ultra-rare disorder with approximately 100 disease-associated variants reported to date. In addition, there are approximately one hundred genes associated with similar epileptic encephalopathy phenotypes. However, since the great majority of pathogenic variants in GRIN2B involve single base pair substitutions, the analytical sensitivity of this test is predicted to be very high (>99%).

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the GRIN2B gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Indications for Test

GRIN2B testing may be considered in patients with early infantile epileptic encephalopathy and developmental delay. Targeted testing is indicated for family members of patients who have a known pathogenic variant in GRIN2B.

Gene

Official Gene Symbol OMIM ID
GRIN2B 138252
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Autism Spectrum Disorders (ASD) Panel
Early Infantile Epileptic Encephalopathy Panel

Citations

  • Endele et al. 2010. PubMed ID: 20890276
  • Genome Aggregation Database (gnomAD)
  • Hu et al. 2016. PubMed ID: 27818011
  • Karczewski et al. 2020. PubMed ID: 32461654
  • Kutsuwada et al. 1996. PubMed ID: 8789948
  • Platzer et al. 2017. PubMed ID: 28377535
  • Soto et al. 2019. PubMed ID: 31213567
  • Swanger et al. 2016. PubMed ID: 27839871

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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