Walker-Warburg Syndrome via the POMT2 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
4841 POMT2 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
4841POMT281406 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 POMT2 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 (van Reeuwijk et al. J Med Genet. 42:907-912, 2005). Other patients with POMT2 variants present with muscle-eye-brain disease (MEB; OMIM 253280; Mercuri et al. Neuromuscul Disord 16:446-448, 2006), while still others present with congenital muscular dystrophy (CMD) (Yanagisawa et al. Neurol 69:1254-1260,2007) or limb girdle muscular dystrophy (LGMD) (Godfrey et al. Brain 130:2725-2735, 2007). Brain involvement appears to be a consistent finding in cases due to POMT2 variants.

Genetics

The dystroglycanopathies are inherited in an autosomal recessive manner. Protein O-mannosyltransferase 2 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). The POMT2 p.Tyr666Cys variant has been found repeatedly in CMD cases (Yanagisawa et al. Neurol 69:1254-1260 2007). Other missense, splice site and nonsense variants are distributed throughout the gene (POMT2 @ www.dmd.nl). It should be noted that five other genes (POMT1, POMGNT1, FCMD, FKRP, and LARGE) encode proteins required for processing of ADG.

Clinical Sensitivity - Sequencing with CNV PG-Select

Variants in POMT2 gene were found in ~10% of a patient cohort having clinical indications of CMD or LGMD, who demonstrated hypoglycosylation of ADG in muscle (Godfrey et al. Brain 130:2725-2735, 2007). Because dystroglycanopathies exhibit extensive locus and allelic heterogeneity, a negative POMT2 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 POMT2 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, CMD, or LGMD with MR 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 POMT2.

Gene

Official Gene Symbol OMIM ID
POMT2 607439
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
  • Mercuri, E., et.al. (2005). "Extreme variability of skeletal and cardiac muscle involvement in patients with mutations in exon 11 of the lamin A/C gene." Muscle Nerve 31(5): 602-9. PubMed ID: 15770669
  • 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
  • van Reeuwijk, J., et.al. (2005). "POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome." J Med Genet 42(12): 907-12. PubMed ID: 15894594
  • Yanagisawa, A., et.al. (2007). "New POMT2 mutations causing congenital muscular dystrophy: identification of a founder mutation." Neurology 69(12): 1254-60. PubMed ID: 17634419

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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