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Megalencephaly-Polymicrogyria-Polydactyly-Hydrocephalus Syndrome 1 via the PIK3R2 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
13351 PIK3R2 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13351PIK3R281479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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 platform).

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

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1 is a rare and early onset neurological disorder. The major symptoms include macrocephaly, megalencephaly, ventriculomegaly, hydrocephalus, cortical malformations, polymicrogyria, focal pachygyria, focal cortical dysplasiacorpus, callosum hyperplasia, profound intellectual disability, seizures and postaxial polydactyly. In certain cases, patients also present other symptoms such as duplicated kidneys, heart malformations and Asperger-like features. Brain MRI reveals megalencephaly, ventriculomegaly and other brain malformations (Mirzaa et al. 2015. PubMed ID: 26520804; Nakamura et al. 2014. PubMed ID: 23745724; Negishi et al. 2017. PubMed ID: 28086757; Terrone et al. 2016. PubMed ID: 26860062).   

As megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome can be caused by defects in a number of genes (AKT3, CCND2, and PIK3R2) with variable and overlapping presentations, the disorder can be difficult to diagnose by clinical manifestation and image studies only. An accurate molecular diagnosis is critical for treatment, prognosis, prediction of recurrence risk, as well as future family planning.

Genetics

PIK3R2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1 is inherited in autosomal dominant mannerPathogenic variants in PIK3R2 include missense and small and large deletions, with missense being the majority (Human Gene Mutation Database). De novo variants are common (Terrone et al. 2016. PubMed ID: 26860062; Quinlan-Jones et al. 2019. PubMed ID: 30293990). Somatic mosaicism of PIK3R2 has also been documented in several studies (Tapper et al. 2014. PubMed ID: 24497998; Mirzaa et al. 2015. PubMed ID: 26520804)In one study, 12 patients had constitutional pathogenic variants, whereas 8 patients had mosaic pathogenic variants (Mirzaa et al. 2015. PubMed ID: 26520804). PIK3R2 has been cited as a conditionally essential gene for growth of human tissue culture cells (Online Gene Essentiality, ogee.medgenius.info).

PIK3R2 encodes phosphatidylinositol 3-kinase, regulatory subunit 2, a core component of the phosphatidylinositol-3-kinase (PI3K)-AKT-mTOR pathway in vascular, limb and brain development (Rivière et al. 2012. PubMed ID: 22729224; Negishi et al. 2017. PubMed ID: 28086757). Functional analysis of pathogenic variants in PIK3R2 showed a significant increase of Phospho-S6 protein activity. The Phospho-S6 protein is an indicator of pathway activation, because it is downstream of the mTOR pathway. This is consistent with the mechanism that elevated PI3K-AKT-MTOR signaling results in brain overgrowth disorders (Negishi et al. 2017. PubMed ID: 28086757). In addition, knock out mice model showed enhanced T cell proliferation due to lack of functional PIK3R2 gene (Deane et al. 2004. PubMed ID: 15153476). PIK3R2-related disorder is a relatively rare cause of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome (Rivière et al. 2012. PubMed ID: 22729224; Negishi et al. 2017. PubMed ID: 28086757).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity of PIK3R2 in a large cohort of patients with PIK3R2-related disorder relevant phenotypes is unavailable in the literature because most studies are case reports. However, pathogenic variants in this gene are a rare cause of megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. Analytical sensitivity should be high.

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 PIK3R2 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.

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

This test is recommended for patients suspected to have PIK3R2-related megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome-1Targeted testing is indicated for family members of patients who have a known pathogenic variant in PIK3R2.

Gene

Official Gene Symbol OMIM ID
PIK3R2 603157
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Deane et al. 2004. PubMed ID: 15153476
  • Human Gene Mutation Database (Biobase).
  • Mirzaa et al. 2015. PubMed ID: 26520804
  • Nakamura et al. 2014. PubMed ID: 23745724
  • Negishi et al. 2017. PubMed ID: 28086757
  • Online Gene Essentiality (OGEE).
  • Quinlan-Jones et al. 2019. PubMed ID: 30293990
  • Rivière et al. 2012. PubMed ID: 22729224
  • Tapper et al. 2014. PubMed ID: 24497998
  • Terrone et al. 2016. PubMed ID: 26860062

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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View Ordering Instructions

1) Select Test Method (Platform)


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.
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