Walker-Warburg Syndrome via the POMGNT1 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
7789 POMGNT1 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7789POMGNT181406 81406(x1), 81479(x1) $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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Variants in the POMGNT1 gene cause muscular dystrophies in the dystroglycanopathy spectrum. Walker-Warburg syndrome (WWS; OMIM 236670), a severe congenital muscular dystrophy with defective neuronal migration and associated structural brain and eye abnormalities, is the most severe manifestation. Other patients with POMGNT1 variants present with muscle-eye-brain disease (MEB; OMIM 253280), while still others present with a severe form of Fukuyama congenital muscular dystrophy (FCMD; OMIM 253800, Godfrey et al. Brain 130:2725-2735, 2007).

Genetics

The dystroglycanopathies are inherited in an autosomal recessive manner. Protein O-mannose beta-1,2-N-acetylglucosaminyltransferase activity is necessary for proper post-translational processing of the protein, alpha dystroglycan (ADG). In the absence of this enzyme, ADG remains hypoglycosylated and diverse pathologies follow (Barresi and Campbell. J Cell Sci 119:199-207, 2006). Molecular diagnosis (and classification) of the dystroglycanopthy subtypes is complex, because extensive locus heterogeneity exists for each disorder (Godfrey et al. Brain 130:2725-2735, 2007), and because the phenotypes caused by the six demonstrated and putative glycosyltransferase genes continue to expand (see for example van Reeuwijk et al. Hum Mut 27:453-459, 2006). Evaluation of a patient’s muscle biopsy by immunofluorescence can detect abnormal glycosylation of ADG and can, therefore, help direct a diagnostic evaluation. It should be noted that five other genes (POMT1, POMT2, FCMD, FKRP, and LARGE) also encode proteins required for processing of ADG.

Clinical Sensitivity - Sequencing with CNV PG-Select

POMGNT1 variants were found in approximately 7% of a patient cohort with ADG hypoglycosylation in muscle (Godfrey et al. Brain 130:2725-2735, 2007). Clinical phenotypes included WWS, MEB-FCMD, and LGMD without mental retardation. Missense, small deletions and duplications, and nonsense variants are distributed throughout the gene (POMGNT1 @ www.dmd.nl). Because dystroglycanopathies exhibit extensive locus and allelic heterogeneity, a negative POMGNT1 sequence result does not rule out a diagnosis of one of these disorders when classic clinical findings are present. If a muscle biopsy is available, immunostaining may also be an appropriate diagnostic approach.

Testing Strategy

This test provides full coverage of all coding exons of the POMGNT1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with symptoms consistent with WWS, MEB, or severe FCMD and 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 POMGNT1.

Gene

Official Gene Symbol OMIM ID
POMGNT1 606822
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Barresi, R. and Campbell, K. P. (2006). "Dystroglycan: from biosynthesis to pathogenesis of human disease." J Cell Sci 119(Pt 2): 199-207. PubMed ID: 16410545
  • Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B, Straub V, Robb S, Quinlivan R, Feng L, Jimenez-Mallebrera C, Mercuri E, et al. 2007. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 130: 2725–2735. PubMed ID: 17878207
  • Reeuwijk J van, Maugenre S, Elzen C van den, Verrips A, Bertini E, Muntoni F, Merlini L, Scheffer H, Brunner HG, Guicheney P, Bokhoven H van. 2006. The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation. Human Mutation 27: 453–459. PubMed ID: 16575835

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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