Walker-Warburg Syndrome via the POMT1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7339 | POMT1 | 81406 | 81406,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
Clinical Features and Genetics
Clinical Features
Variants in the POMT1 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 POMT1 variants present with muscle-eye-brain disease (MEB; OMIM 253280), while still others present with congenital or limb girdle muscular dystrophy with associated mental retardation (MR) but without structural brain abnormalities (LGMD2K, OMIM 609308 and CMD-MR, respectively) (Godfrey et al. Brain 130:2725-2735, 2007).
Genetics
The dystroglycanopathies are inherited in an autosomal recessive manner. Protein O-mannosyltransferase 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). Missense, frameshift, and nonsense variants are distributed throughout the gene (POMT1 @ www.dmd.nl). 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 (POMT2, POMGNT1, FCMD, FKRP, and LARGE) encode proteins also required for processing of ADG.
Clinical Sensitivity - Sequencing with CNV PG-Select
Protein O-mannosyltransferase 1 is a glycosyltransferase encoded by POMT1, and variants in this gene have been found in 7%-20% of WWS patients (Beltran-Valero de Bernabe et al. Am J Hum Genet 71:1033-1043, 2002; Currier et al. Am J Med Genet A. 133A:53-57, 2005). Because dystroglycanopathies exhibit extensive locus and allelic heterogeneity, a negative POMT1 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 POMT1 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-MR, 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 POMT1.
Individuals with symptoms consistent with WWS, MEB, CMD-MR, 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 POMT1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| POMT1 | 607423 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
Related Test
| Name |
|---|
| Walker-Warburg Syndrome via the Glycosyltransferase-Like Domain-Containing Protein 2 (POMGNT2) Gene |
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
- Beltran-Valero de Bernabe, D., et.al. (2002). "Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome." Am J Hum Genet 71(5): 1033-43. PubMed ID: 12369018
- Currier, S. C., et.al. (2005). "Mutations in POMT1 are found in a minority of patients with Walker-Warburg syndrome." Am J Med Genet A 133A(1): 53-7. PubMed ID: 15637732
- 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
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
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