Walker-Warburg Syndrome via the Glycosyltransferase-Like Domain-Containing Protein 2 (POMGNT2) 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
8703 POMGNT2 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8703POMGNT281479 81479(x2) $890 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. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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).

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

For Sanger Sequencing click here.

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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy in which seven causative genes have been previously identified. These genes are POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE, and ISPD, each of which is believed to be involved in post translational modification of the sarcolemma-spanning protein alpha dystroglycan (ADG). Loss of function of any of the seven genes results in hypoglycosylation of ADG and reduced binding of ADG to the basal lamina through laminin (Barresi and Campbell 2006). WWS is the most severe form of ADG-related congenital muscular dystrophy, presenting with profound hypotonia, defective neuronal migration and associated structural brain and eye abnormalities. Central nervous system findings include cobblestone lissencephaly, cerebellar malformations, microophthalmia and cataracts. Patients have profound mental retardation and typically die in the first year of life. Muscle biopsies demonstrate a dystrophic process and markedly reduced or absent staining with antibodies to the glycolepitope of ADG. The seven genes referenced above account for only approximately half of all cases of WWS. A newly discovered gene, POMGNT2 (OMIM 614828), has been shown to lead to WWS in a small number of consanguineous families, and to recapitulate many of the clinical features of WWS in an animal model (Manzini et al. 2012).

Genetics

Mutations in the POMGNT2 gene are the eighth documented cause of Walker-Warburg syndrome (Manzini et al. 2012). POMGNT2 encodes a protein with a putative glycosyltransferase domain, consistent with the function of most other alpha dystroglycanopathy genes. POMGNT2-related WWS is inherited in an autosomal recessive manner. POMGNT2 mutations reported thus far include nonsense and missense mutations.

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity cannot be estimated at this time because of the small number of reported cases with POMGNT2 mutations. Analytical sensitivity may be high because the mutations reported to date are all detectable by this method.

Testing Strategy

This test provides full coverage of all coding exons of the POMGNT2 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

Individuals with symptoms consistent with Walker-Warburg syndrome. Individuals with immunofluorescence results demonstrating hypoglycosylation of ADG in muscle. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in POMGNT2.

Gene

Official Gene Symbol OMIM ID
POMGNT2 614828
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Walker-Warburg Congenital Muscular Dystrophy AR 236670

Citations

  • Barresi R, Campbell K. 2006. Dystroglycan: from biosynthesis to pathogenesis of human disease. J. Cell Sci. 119:199-207. PubMed ID: 16410545
  • Manzini MC, Tambunan DE, Hill RS, Yu TW, Maynard TM, Heinzen EL, Shianna KV, Stevens CR, Partlow JN, Barry BJ, Rodriguez J, Gupta VA, et al. 2012. Exome Sequencing and Functional Validation in Zebrafish Identify GTDC2 Mutations as a Cause of Walker-Warburg Syndrome. The American Journal of Human Genetics 91: 541–547. PubMed ID: 22958903

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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