Congenital Disorders of Glycosylation (CDG) Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10625 ALG1 81479,81479 Order Options and Pricing
ALG11 81479,81479
ALG12 81479,81479
ALG13 81479,81479
ALG2 81479,81479
ALG3 81479,81479
ALG6 81479,81479
ALG8 81479,81479
ALG9 81479,81479
ATP6AP1 81479,81479
ATP6V0A2 81479,81479
B4GALT1 81479,81479
CCDC115 81479,81479
COG1 81479,81479
COG2 81479,81479
COG4 81479,81479
COG5 81479,81479
COG6 81479,81479
COG7 81479,81479
COG8 81479,81479
DDOST 81479,81479
DHDDS 81479,81479
DOLK 81479,81479
DPAGT1 81479,81479
DPM1 81479,81479
DPM2 81479,81479
DPM3 81479,81479
GMPPA 81479,81479
GNE 81406,81479
MAGT1 81479,81479
MAN1B1 81479,81479
MGAT2 81479,81479
MOGS 81479,81479
MPDU1 81479,81479
MPI 81405,81479
NGLY1 81479,81479
PGM1 81479,81479
PMM2 81479,81479
RFT1 81479,81479
SLC35A1 81479,81479
SLC35A2 81479,81479
SLC35C1 81479,81479
SLC39A8 81479,81479
SRD5A3 81479,81479
SSR4 81479,81479
STT3A 81479,81479
STT3B 81479,81479
TMEM165 81479,81479
TMEM199 81479,81479
TUSC3 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10625Genes x (50)81479 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Congenital disorders of glycosylation (CDGs) are a clinically heterogeneous group of inborn errors of metabolism that are characterized by defects in protein or lipid glycosylation, a form of post-translational modification. These disorders can be further differentiated into several categories depending upon what part of the glycosylation pathway has been disrupted: protein N-linked protein glycosylation defects, which are the most common; O-linked protein glycosylation defects; glycolipid and glycosylphosphatidylinositol (GPI) anchor defects; or multi-pathway defects (Brasil et al. 2018. PubMed ID: 29702557; Jaeken. 2017. PubMed ID: 28484880; Scott et al. 2014. PubMed ID: 24831587). Analysis via serum transferrin isoelectrofocusing is often considered the standard first screen test for N-linked protein glycosylation disorders; however, normal results with this test do not preclude the possibility of a CDG diagnosis (N-linked or otherwise), and therefore molecular testing is often advised if a CDG is part of the differential (Jaeken. 2017. PubMed ID: 28484880).

As detective glycosylation negatively impacts a wide variety of cellular processes, most of these diseases are multi-systemic and early onset in nature. However, varying degrees of severity and age at onset have been described, even in patients with defects in the same gene (Sparks and Krasnewich. 2015. PubMed ID: 20301289; Sparks and Krasnewich. 2017. PubMed ID: 20301507). The majority of N-linked CDGs present in infancy, and symptoms may include failure to thrive, developmental delay, liver dysfunction, seizures, hypotonia, hypoglycemia, protein-losing enteropathy, eye dysfunction (such as strabismus or retinitis pigmentosa), immunologic dysfunction, skin abnormalities, and/or skeletal abnormalities (Sparks and Krasnewich. 2017. PubMed ID: 20301507).

CDG type Ia (PMM2-CDG) due to pathogenic variants in PMM2 is the most common N-linked CDG described to date. The clinical spectrum of PMM2-CDG may range from a severe infantile-onset multi-system disease to an adult stable disability disorder (Sparks and Krasnewich. 2015. PubMed ID: 20301289).

O-linked CDGs, in contrast, typically present as muscular dystrophies with additional phenotypes such as hypotonia, brain malformations, intellectual disability, cardiac involvement, and/or ocular dysfunction (Martin. 2005. PubMed ID: 16584074).

GPI anchor defects are characterized by intellectual disability, hyperphosphatasia, and/or paroxysmal nocturnal hemoglobinuria (Witters et al. 2017. PubMed ID: 29112118). Lastly, defects that result in multi-pathway dysfunction, such as those that involve the dolichol phosphate mutase (DPM) complex that is essential for all three glycosylation pathways, often result in severe multi-system phenotypes. Clinical features may overlap with symptoms seen in both N- and O-linked glycosylation disorders (Witters et al. 2017. PubMed ID: 29112118).

At this time, treatment is available for MPI-CDG (oral mannose and/or liver transplantation) (Jaeken. 2017. PubMed ID: 28484880). Partial treatments exist for SLC35C1-CDG (oral fucose); DOLK-CDG (heart transplantation); PGM1-CDG, SLC35A2-CDG, and SLC39A8-CDG (galactose); and DPAGT1-CDG and ALG2-CDG (cholinesterase inhibitors) (Jaeken. 2017. PubMed ID: 28484880).

Genetics

The great majority of CDGs tested in this panel exhibit autosomal recessive inheritance, with a few exceptions: notably, ALG13, ATP6AP1, MAGT1, SLC35A2, and SSR4 exhibit X-linked inheritance (Sparks and Krasnewich. 2017. PubMed ID: 20301507; Evers et al. 2017. PubMed ID: 28688840). See individual gene test descriptions for additional information regarding gene function and pathogenic variant spectra.

Note that the most common pathogenic variant in PMM2, p.Arg141His, has a very high carrier rate in certain populations (up to ~0.8% in European continental populations, http://gnomad.broadinstitute.org/), yet homozygotes for this variant have not yet been documented. Homozygotes are therefore strongly suspected to be embryonically lethal (Matthijs et al. 1998. PubMed ID: 9497260; Thiel et al. 2006. PubMed ID: 16847317).

Clinical Sensitivity - Sequencing with CNV PGxome

Clinical sensitivity for this panel is difficult to estimate at this time, as this specific group of genes has not previously been tested in a large cohort to date. The majority of CDGs have only been reported in a handful of individuals; some exceptions include CDG caused by defects in the PMM2 gene, which has been reported in over 700 individuals to date and CDG due to pathogenic variants in the MPI, ALG6, SRD5A3, and COG6 genes (Sparks and Krasnewich. 2017. PubMed ID: 20301507).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.8% coverage of all coding exons of the genes 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 coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Individuals with clinical symptoms that are consistent with a suspected underlying congenital disorder of glycosylation (CDG) or individuals with diagnostic serum transferrin isoform results are candidates for this test.

Diseases

Name Inheritance OMIM ID
Alacrima, Achalasia, and Mental Retardation Syndrome AR 615510
Carbohydrate-Deficient Glycoprotein Syndrome Type II AR 212066
Congenital Disorder of Deglycosylation AR 615273
Congenital Disorder Of Glycosylation Type 1A AR 212065
Congenital Disorder Of Glycosylation Type 1B AR 602579
Congenital Disorder Of Glycosylation Type 1C AR 603147
Congenital Disorder Of Glycosylation Type 1D AR 601110
Congenital Disorder Of Glycosylation Type 1E AR 608799
Congenital Disorder Of Glycosylation Type 1F AR 609180
Congenital Disorder Of Glycosylation Type 1G AR 607143
Congenital Disorder Of Glycosylation Type 1H AR 608104
Congenital Disorder Of Glycosylation Type 1I AR 607906
Congenital Disorder Of Glycosylation Type 1J AR 608093
Congenital Disorder Of Glycosylation Type 1K AR 608540
Congenital Disorder Of Glycosylation Type 1L AR 608776
Congenital Disorder Of Glycosylation Type 1M AR 610768
Congenital Disorder Of Glycosylation Type 1O AR 612937
Congenital Disorder Of Glycosylation Type 1P AR 613661
Congenital Disorder Of Glycosylation Type 1Q AR 612379
Congenital Disorder Of Glycosylation Type 2C AR 266265
Congenital Disorder Of Glycosylation Type 2D AR 607091
Congenital Disorder Of Glycosylation Type 2E AR 608779
Congenital Disorder Of Glycosylation Type 2F AR 603585
Congenital Disorder Of Glycosylation Type 2G AR 611209
Congenital Disorder Of Glycosylation Type 2I AR 613612
Congenital Disorder Of Glycosylation Type IIb AR 606056
Congenital Disorder Of Glycosylation Type IIh AR 611182
Congenital Disorder Of Glycosylation Type IIj AR 613489
Congenital Disorder of Glycosylation Type IIk AR 614727
Congenital Disorder of Glycosylation Type IIl AR 614576
Congenital Disorder of Glycosylation Type IIm XL 300896
Congenital Disorder of Glycosylation Type IIn AR 616721
Congenital Disorder of Glycosylation Type IIo AR 616828
Congenital Disorder of Glycosylation Type IIp AR 616829
Congenital Disorder of Glycosylation Type IIq AR 617395
Congenital Disorder Of Glycosylation Type In AR 612015
Congenital Disorder of Glycosylation Type Ir AR 614507
Congenital Disorder of Glycosylation Type It AR 614921
Congenital Disorder of Glycosylation Type Iu AR 615042
Congenital Disorder of Glycosylation Type Iw AR 615596
Congenital Disorder of Glycosylation Type Ix AR 615597
Congenital Disorder of Glycosylation Type Iy XL 300934
Cutis Laxa, Autosomal Recessive, Type IIA AR 219200
Epileptic Encephalopathy, Early Infantile, 36 XL 300884
GNE Myopathy AR 605820
Immunodeficiency and Hepatopathy with Cutis Laxa XL 300972
Immunodeficiency, X-Linked, With Magnesium Defect, Epstein-Barr Virus Infection, And Neoplasia XL 300853
Mental Retardation, Autosomal Recessive 15 AR 614202
Mental Retardation, Autosomal Recessive 7 AR 611093
Retinitis Pigmentosa 59 AR 613861
Sialuria AD 269921
Wrinkly Skin Syndrome AR 278250

Related Test

Name
PGxome®

Citations

  • Brasil et al. 2018. PubMed ID: 29702557
  • Evers et al. 2017. PubMed ID: 28688840
  • Jaeken and Péanne. 2017. PubMed ID: 28484880
  • Martin. 2005. PubMed ID: 16584074
  • Matthijs et al. 1998. PubMed ID: 9497260
  • Scott et al. 2014. PubMed ID: 24831587
  • Sparks and Krasnewich. 2015. PubMed ID: 20301289
  • Sparks and Krasnewich. 2017. PubMed ID: 20301507
  • Thiel et al. 2006. PubMed ID: 16847317
  • Witters et al. 2017. PubMed ID: 29112118

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.

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

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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.

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