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Epilepsy: Early Infantile Epileptic Encephalopathy via the ARHGEF9 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
4095 ARHGEF9 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4095ARHGEF981479 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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Early Infantile Epileptic Encephalopathy (EIEE) is a clinically and genetically heterogeneous neurodevelopmental disorder. The key feature of EIEE is onset of frequent and/or severe seizures within the first few weeks of life (Noh et al., 2012. PubMed ID: 22342633).

ARHGEF9-related early infantile epileptic encephalopathy is a rare genetic cause for early infantile epilepsy with onset at birth or early infancy. The common symptoms of this disorder include delayed motor development, severe tonic and hyperekplectic seizures, hypertonia, intellectual disability and a particular facial dysmorphic feature. Brain MRI shows normal or brain atrophy, hypoplastic frontal lobe, hippocampal sclerosis, frontal polymicrogyria in the patients. Male patients have severe symptoms, whereas heterozygous females are unaffected (Shimojima et al., 2011. PubMed ID: 21633362). However, female cases with intellectual disability have been reported due to de novo large deletions or translocations or inversions that interrupt the ARHGEF9 gene and skewed X inactivation. Patients have variable responses to antiepileptic drugs (Alber et al., 2017. PubMed ID: 28589176; Shimojima et al., 2011. PubMed ID: 21633362; Marco et al., 2009. PubMed ID: 21731583).

Genetics

ARHGEF9-related early infantile epileptic encephalopathy is inherited in an X-linked recessive manner. It is caused by pathogenic variants in the ARHGEF9 gene encoding collybistin, a brain-specific GDP/GTP-exchange factor. Collybistin is required for both the initial formation and maintenance of gephyrin and gephyrin-dependent GABAA receptor clusters at inhibitory post-synapses in certain regions of the forebrain (Papadopoulos and Soykan, 2011. PubMed ID: 21738498).

Pathogenic variants in ARHGEF9 include missense, nonsense, splicing variants, large deletions and complex rearrangements involving the ARHGEF9 locus (Human Gene Mutation Database; Alber et al., 2017. PubMed ID: 28589176). De novo pathogenic variants in ARHGEF9 gene are common and include point variants, large deletions, translocations, and inversions (Alber et al., 2017. PubMed ID: 28589176).

Clinical Sensitivity - Sequencing with CNV PG-Select

In one study of males with severe intellectual disability (ID) and epilepsy of unknown cause, 4% (1 in 23) of cases were found to be caused by single nucleotide variations in ARHGEF9 (Shimojima et al., 2011. PubMed ID: 21633362). Another study of males and females with ID of unknown cause identified pathogenic ARHGEF9 variants in 4% of males (2 of 47) (de Ligt et al., 2012. PubMed ID: 23033978).

In a review of the phenotypic and genotypic spectrum of ARHGEF9 pathogenic variants, 7 out of 18 cases were found to be caused by large deletions, inversions, translocations or other complex arrangements involving ARHGEF9 (Alber et al., 2017. PubMed ID: 28589176).

Testing Strategy

This test provides full coverage of all coding exons of the ARHGEF9 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

The test is recommended for patients suspected to have ARHGEF9-related early infantile epileptic encephalopathy.

Gene

Official Gene Symbol OMIM ID
ARHGEF9 300429
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Epileptic Encephalopathy, Early Infantile, 8 XL 300607

Citations

  • Alber et al., 2017. PubMed ID: 28589176
  • de Ligt et al., 2012. PubMed ID: 23033978
  • Human Gene Mutation Database (Bio-base).
  • Marco et al., 2009. PubMed ID: 21731583
  • Noh et al., 2012. PubMed ID: 22342633
  • Papadopoulos and Soykan, 2011. PubMed ID: 21738498
  • Shimojima et al., 2011. PubMed ID: 21633362

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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