DNA icon

Congenital Disorders of Glycosylation, Type Io Plus Secondary Dystroglycanopathy via the DPM3 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
9085 DPM3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9085DPM381479 81479,81479 $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

  • Kym Bliven, PhD

Clinical Features and Genetics

Clinical Features

Congenital disorders of glycosylation (CDGs) are a genetically heterogeneous group of disorders caused by defective synthesis of N-linked glycans. Abnormalities in these glycoconjugates cause disturbances in metabolism, cell recognition, cell adhesion, protease resistance, host defense, cell migration, and antigenicity (Marquardt and Denecke. Eur J Pediat 162:359-379, 2003). Clinical presentations are characterized by multisystem involvement. Dystroglycan is the central component of the muscle dystrophin-glycoprotein complex ([DGC] Michele and Campbel.l J Biol Chem 278:15457-15460, 2003). DAG1 encodes the alpha and beta subunits of dystroglycan. Both subunits undergo modification by N- and O-linked glycosylation; however, alpha-dystroglycan undergoes extensive O-linked glycosylation (Ibraghimov-Beskrovnaya et al. Hum Mol Genet 2:1651-1657, 1993). The glycosylation status of dystroglycan is critical for ligand binding and pathogenesis (Barresi and Campbell. J Cell Sci 119:199-207, 2006). A patient with clinical symptoms consistent with muscular dystrophy and a muscle biopsy with immunohistochemical signs of dystroglycanopathy was found to have an abnormal serum transferrin profile, suggesting a CDG type I pattern and reduced dolichol-phosphate-mannose (Dol-P-Man) synthase activity secondary to a homozygous DPM3 (OMIM 605951) variant (Leifeber et al. Am J Hum Genet 85:76-86, 2009). DPM3 encodes a Golgi membrane-spanning protein that binds the catalytic subunit of the Dol-P-Man enzyme. Variants in DPM1, the catalytic subunit of Dol-P-Man, have been shown to cause CDG Ie (OMIM 608799), but no other connections between muscular dystrophy and N-linked glycosylation defects have ever been made. DPM3-associated CDG has been classified as type Io (OMIM 612937).

Genetics

Congenital disorders of glycosylation and the dystroglycan-associated muscular dystrophies all exhibit autosomal recessive inheritance. Thirteen forms of CDG have been characterized at the molecular level but only three, CDG Ia, CDG Ib, and CDG Ic, have been reported in more than a small number of patients. Congenital and limb girdle muscular dystrophy caused by defective posttranslational processing of alpha-dystroglycan results from variants in six genes that encode known or putative glycosyltransferases. Yet unidentified genes are likely the cause for at least half of all dystroglycanopathy cases. The CDGs result from defective N-linked glycosylation while the dystroglycan-associated muscular dystrophies result from defective O-linked glycosylation. The single patient with apparent dystroglycanopathy and reduced Dol-P-Man synthase activity was found to have a homozygous p.Leu85Ser variant in the DPM3 gene manifesting as reduced binding of the catalytic domain to the Golgi membrane (Leifeber et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the low incidence of this disorder, clinical sensitivity cannot be estimated.

Testing Strategy

This test provides full coverage of all coding exons of the DPM3 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 biochemical findings consistent with type I CDG and clinical and immunohistochemical findings consistent with secondary dystroglycanopathy. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DPM3.

Gene

Official Gene Symbol OMIM ID
DPM3 605951
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Congenital Disorder Of Glycosylation Type 1O 612937

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
  • Ibraghimov-Beskrovnaya, O., et.al. (1993). "Human dystroglycan: skeletal muscle cDNA, genomic structure, origin of tissue specific isoforms and chromosomal localization." Hum Mol Genet 2(10): 1651-7. PubMed ID: 8268918
  • Leifeber et al. Am J Hum Genet 85:76-86, 2009 PubMed ID: 19576565
  • Leifeber et al. Am J Hum Genet 85:76-86, 2009 PubMed ID: 19576565
  • Marquardt, T., Denecke, J. (2003). "Congenital disorders of glycosylation: review of their molecular bases, clinical presentations and specific therapies." Eur J Pediatr 162(6): 359-79. PubMed ID: 12756558
  • Michele, D. E., Campbell, K. P. (2003). "Dystrophin-glycoprotein complex: post-translational processing and dystroglycan function." J Biol Chem 278(18): 15457-60. PubMed ID: 12556455

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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×