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Epilepsy: GNAO1-Related Early Infantile Epileptic Encephalopathy and Neurodevelopmental Disorder with Involuntary Movement via the GNAO1 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
GNAO1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5489GNAO181479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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).

GNAO1-related early infantile epileptic encephalopathy is a rare genetic cause for early infantile epilepsy with median age of onset of 10 months (range 0–48 months). Major symptoms include intractable tonic seizures, absence of speech, severe motor and cognitive impairment with early postnatal lethality. Some patients present involuntary movements, hyperkinetic movements, facial dyskinesia, dysphagia, dystonia, chorea, athetosis and hyperalgesia. Initial EEG shows suppression-burst pattern, while MRI presents structural brain abnormalities including cerebral atrophy, corpus callosum dysgenesis and delayed myelination. Patients could be diagnosed as Ohtahara syndrome. Most patients are resistant to drug treatment, however, tetrabenazine and deep brain stimulation may be considered for treatments of dyskinesia (Nakamura et al. 2013. PubMed ID: 23993195; Danti et al. 2017. PubMed ID: 28357411; Marcé-Grau et al. 2016. PubMed ID: 27072799; Saitsu et al. 2016. PubMed ID: 25966631).

Genetics

GNAO1-related early infantile epileptic encephalopathy and neurodevelopmental disorder with involuntary movement is inherited in an autosomal dominant manner. The disease is caused by pathogenic variants in the GNAO1 gene encoding guanine nucleotide-binding protein alpha activating activity polypeptide O (in the family of G protein, Gαo). In mammals, Gαo protein is a polypeptide in the group of alpha subunit (Gα). Gα subunit is bound to guanosine diphosphate (GDP) and forms the Gαβγ heterotrimeric complex. The Gαo protein is highly expressed in brain. Through G protein conducted signaling pathway, Gαo play important roles in maintaining normal brain function (Nakamura et al. 2013. PubMed ID: 23993195).

Pathogenic variants in GNAO1 only include missense and a deletion of 15 nucleotides. No large deletions/duplications in the GNAO1 locus have been reported (Human Gene Mutation Database). De novo pathogenic variants in GNAO1 gene are common (Nakamura et al. 2013. PubMed ID: 23993195; Marcé-Grau et al. 2016. PubMed ID: 27072799).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a study of severe early infantile Epileptic Encephalopathy in patients diagnosed with Ohtahara Syndrome, 33% (4 out of 12) of cases were found to be caused by de novo pathogenic variants in GNAO1 (Nakamura et al. 2013. PubMed ID: 23993195).

To our knowledge, only a deletion of 15 nucleotides has been reported to date, which can be detected by sequencing (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GNAO1 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 GNAO1-related early infantile epileptic encephalopathy.

Gene

Official Gene Symbol OMIM ID
GNAO1 139311
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Danti et al. 2017. PubMed ID: 28357411
  • Human Gene Mutation Database (Bio-base).
  • MarcÚ-Grau et al. 2016. PubMed ID: 27072799
  • Nakamura et al. 2013. PubMed ID: 23993195
  • Noh et al. 2012. PubMed ID: 22342633
  • Saitsu et al. 2016. PubMed ID: 25966631

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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