Congenital Disorders of Glycosylation, Type Ib (CDG Ib) via the MPI 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 | |
|---|---|---|---|---|---|
| 7907 | MPI | 81405 | 81405,81479 | $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
Congenital disorders of glycosylation (CDG) are a genetically heterogeneous group of disorders caused by defective synthesis of asparagine (N)-linked glycans. Abnormalities in these glycoconjugates result in disturbed metabolism, cell recognition, cell adhesion, protease resistance, host defense, cell migration, and antigenicity (Marquardt and Denecke. Eur J Pediat 162:359-379, 2003). Consequently, clinical presentations are characterized by multisystem involvement. Individuals with CDG Ib (OMIM 602579) exhibit diarrhea, protein-losing enteropathy, profound hypoglycemia, coagulopthy, and fibrotic liver disease (see for example Jaeken et al. Am J Hum Genet 62:1535-1539, 1998). Patients are not dysmorphic and do not have cerebellar hypoplasia or unusual fat distribution as often seen in CDG Ia patients. CDG Ib is treatable with oral mannose (Niehues at al. J Clin Invest 101:1414-1420, 1998) by virtue of an alternate pathway of mannose to mannose-6-phophate catalyzed by hexokinase (Schollen et al. Hum Mut 16: 247-252, 2000).
Genetics
All CDGs 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 individual patients. CDG Ia is the most common form with ~400 cases reported worldwide, followed by CDG 1b and CDG Ic, each with approximately 20 cases reported. The MPI gene (OMIM 154550) codes for mannosephosphate isomerase, the enzyme responsible for interconverting fructose-6-phosphate and mannose-6-phosphate. Its activity is critical to maintain adequate D-mannose derivative levels which are needed for glycosylation reactions. Variants in MPI are distributed throughout the coding region, and missense variants are the most common type observed.
Clinical Sensitivity - Sequencing with CNV PG-Select
In cases with demonstrated reduced activity of mannosephosphate isomerase and diagnostic serum transferrin glycoforms, MPI sequencing is nearly 100% sensitive (Sparks and Krasnewich GeneReviews 2008). Vuillaumier-Barrot et al. reported that an MPI p.Arg295His variant is the cause of CDG Ib in the Saguenay-Lac Saint-Jean region of Quebec (J Med Genet 39:849-851, 2002).
Testing Strategy
This test provides full coverage of all coding exons of the MPI gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Individuals with clinical symptoms consistent with CDG Ib. Individuals with diagnostic serum transferrin isoform results (decreased tetrasialotransferrin and increased asailotransferrin and disialotransferrin). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MPI.
Individuals with clinical symptoms consistent with CDG Ib. Individuals with diagnostic serum transferrin isoform results (decreased tetrasialotransferrin and increased asailotransferrin and disialotransferrin). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MPI.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| MPI | 154550 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Congenital Disorder Of Glycosylation Type 1B | AR | 602579 |
Related Test
| Name |
|---|
| Congenital Disorders of Glycosylation (CDG) Panel (Types Ia, Ib, and Ic) |
Citations
- Jaeken, J., et.al. (1998). "Phosphomannose isomerase deficiency: a carbohydrate-deficient glycoprotein syndrome with hepatic-intestinal presentation." Am J Hum Genet 62(6): 1535-9. PubMed ID: 9585601
- 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
- Niehues, R., et.al. (1998). "Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy." J Clin Invest 101(7): 1414-20. PubMed ID: 9525984
- Schollen, E., et.al. (2000). "Genomic organization of the human phosphomannose isomerase (MPI) gene and mutation analysis in patients with congenital disorders of glycosylation type Ib (CDG-Ib)." Hum Mutat 16(3): 247-52. PubMed ID: 10980531
- Susan E Sparks, Donna M Krasnewich (2008). "Congenital Disorders of Glycosylation Overview."
- Vuillaumier-Barrot, S., et.al. (2002). "Protein losing enteropathy-hepatic fibrosis syndrome in Saguenay-Lac St-Jean, Quebec is a congenital disorder of glycosylation type Ib." J Med Genet 39(11): 849-51. PubMed ID: 12414827
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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ORDER OPTIONS
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