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Periventricular Nodular Heterotopia 7 Via the NEDD4L Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
15415 NEDD4L 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15415NEDD4L81479 81479,81479 $890 Order Options and Pricing

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

NEDD4L-related periventricular nodular heterotopia 7 is a rare neurological disorder with onset at birth or during the prenatal period. The major symptoms include bilateral periventricular nodular heterotopia, severe neurodevelopmental delay, refractory seizures, and perisylvian polymicrogyria, cleft palate, and bilateral toe syndactyly. Minor features include variable dysmorphic facial features, hearing impairment, optic atrophy, contractures, and hypospadias (Stouffs et al. 2020. PubMed ID: 32117442; Broix et al. 2016. PubMed ID: 27694961). In the prenatal period, hypokinesia and flexion contractures can be seen (Elbracht et al. 2018. PubMed ID: 30393983).

As periventricular nodular heterotopia can be caused by defects in many genes with variable and overlapping presentations, it is difficult to diagnose by clinical manifestation and image studies only. An accurate molecular diagnosis is critical for treatment, prognosis, and prediction of recurrence risk as well as future family planning.

Genetics

NEDD4L-related periventricular nodular heterotopia 7 is inherited in an autosomal dominant manner. The vast majority of pathogenic variants in NEDD4L are missense variants. Some variants are located in the HECT domain, and cause deregulation of signaling pathways, such as the AKT/mTOR pathway, whereas others are in the WW domain, which is probably related to the recognition of substrates for ligation (Broix et al. 2016. PubMed ID: 27694961; Stouffs et al. 2020. PubMed ID: 32117442). One large deletion has also been reported in the NEDD4L locus (Human Gene Mutation Database). De novo pathogenic variants are common and parental mosaicism has been reported (Broix et al. 2016. PubMed ID: 27694961). NEDD4L is relatively intolerant to loss of function variants (Genome Aggregation Database).

NEDD4L encodes E3 ubiquitin ligase (Yanpallewar et al. 2016. PubMed ID: 27604420). A mouse model showed that NEDD4L is homogenously expressed in the cortical plate, ventricular zone, and ganglionic eminences (Broix et al. 2016. PubMed ID: 27694961), and deletion of this gene causes perinatal lethality (Yanpallewar et al. 2016. PubMed ID: 27604420).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity of NEDD4L testing is high. However, periventricular nodular heterotopia caused by defects in NEDD4L is rare (Broix et al. 2016. PubMed ID: 27694961).

Testing Strategy

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

This test provides full coverage of all coding exons of the NEDD4L 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

NEDD4L sequencing is recommended for patients suspected to have periventricular nodular heterotopia. Targeted testing is indicated for family members of patients who have a known pathogenic variant in NEDD4L.

Gene

Official Gene Symbol OMIM ID
NEDD4L 606384
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Periventricular Nodular Heterotopia 7 AD 617201

Citations

  • Broix et al. 2016. PubMed ID: 27694961
  • Elbracht et al. 2018. PubMed ID: 30393983
  • Genome Aggregation Database (gnomAD).
  • Stouffs et al. 2020. PubMed ID: 32117442
  • Yanpallewar et al. 2016. PubMed ID: 27604420

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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