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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7907 MPI 81405 81405,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7907MPI81405 81405(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

  • Kym Bliven, PhD

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.

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


Specimen Types

Specimen Requirements and Shipping Details

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
×