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  • Test code: 06155
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
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  • Request a sample kit
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  1. Test Catalog
  2. Invitae Congenital Disorders of Glycosylation Panel

Invitae Congenital Disorders of Glycosylation Panel

Test description

The Invitae Congenital Disorders of Glycosylation Panel analyzes up to 103 genes that are associated with congenital disorders of glycosylation (CDGs). This test is useful for the diagnosis of patients in whom a congenital disorder of glycosylation is suspected due to clinical symptoms or biochemical findings, such as abnormal transferrin isoelectric focusing.

This panel covers:

  • disorders of N-linked glycosylation, including type I and type II
  • conserved oligomeric golgi (COG) complex defects
  • disorder of deglycosylation (NGLY1)

Genes tested

Primary panel

ALG1 ALG11 ALG12 ALG13 ALG2 ALG3 ALG6 ALG8 ALG9 ATP6V0A2 B3GLCT CHST14 COG1 COG2 COG4 COG5 COG6 COG7 COG8 DHDDS DOLK DPAGT1 DPM1 DPM2 DPM3 G6PC3 GFPT1 GMPPA GMPPB MAGT1 MAN1B1 MGAT2 MOGS MPDU1 MPI NGLY1 PGM1 PGM3 PMM2 RFT1 SEC23B SLC35A1 SLC35A2 SLC35C1 SRD5A3 SSR4 ST3GAL5 TMEM165 TRIP11 TUSC3

Add-on Preliminary-evidence Genes for Congenital Disorders of Glycosylation

ALG14 B4GALT1 DDOST NUS1 PIGM RPN2 SEC23A SLC35A3 ST3GAL3 STT3A STT3B

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

Add-on Disorders of O-mannosylation Genes

B3GALNT2 B4GAT1 FKRP FKTN GNE ISPD LARGE1 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1

Disorders of o-mannosylation have defects in o-mannosyl glycan synthesis, mainly of alpha-dystroglycan. These disorders may have overlapping phenotypes with CDGs, including muscular phenotypes, brain malformations, and eye abnormalities. These genes can be included at no additional charge.

Add-on Glycosylation Genes Not Involved in N-glycosylation

B3GALT6 B3GAT3 B4GALNT1 B4GALT7 C1GALT1C1 CHST3 CHST6 CHSY1 DSE EOGT EXT1 EXT1 EXT2 EXT2 GALNT3 LFNG PAPSS2 PIGA PIGL PIGM PIGN PIGO PIGQ PIGT PIGV PIGW POFUT1 POGLUT1 SLC26A2 SLC35D1 XYLT1

Disorders of glycosamine synthesis, glycosphingolipids and o-linked glycosylation may have overlapping phenotypes with CDGs, including delayed motor and speech development, musculoskeletal disorders, skin disorders and immune system defects. These genes can be included at no additional charge.

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Primary panel (50 genes)

ALG1 ALG11 ALG12 ALG13 ALG2 ALG3 ALG6 ALG8 ALG9 ATP6V0A2 B3GLCT CHST14 COG1 COG2 COG4 COG5 COG6 COG7 COG8 DHDDS DOLK DPAGT1 DPM1 DPM2 DPM3 G6PC3 GFPT1 GMPPA GMPPB MAGT1 MAN1B1 MGAT2 MOGS MPDU1 MPI NGLY1 PGM1 PGM3 PMM2 RFT1 SEC23B SLC35A1 SLC35A2 SLC35C1 SRD5A3 SSR4 ST3GAL5 TMEM165 TRIP11 TUSC3

Panel details and technical assay limitations
Add-on Preliminary-evidence Genes for Congenital Disorders of Glycosylation (11 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

ALG14 B4GALT1 DDOST NUS1 PIGM RPN2 SEC23A SLC35A3 ST3GAL3 STT3A STT3B

Panel details and technical assay limitations
Add-on Disorders of O-mannosylation Genes (13 genes)

Disorders of o-mannosylation have defects in o-mannosyl glycan synthesis, mainly of alpha-dystroglycan. These disorders may have overlapping phenotypes with CDGs, including muscular phenotypes, brain malformations, and eye abnormalities. These genes can be included at no additional charge.

B3GALNT2 B4GAT1 FKRP FKTN GNE ISPD LARGE1 POMGNT1 POMGNT2 POMK POMT1 POMT2 RXYLT1

Panel details and technical assay limitations
Add-on Glycosylation Genes Not Involved in N-glycosylation (31 genes)

Disorders of glycosamine synthesis, glycosphingolipids and o-linked glycosylation may have overlapping phenotypes with CDGs, including delayed motor and speech development, musculoskeletal disorders, skin disorders and immune system defects. These genes can be included at no additional charge.

B3GALT6 B3GAT3 B4GALNT1 B4GALT7 C1GALT1C1 CHST3 CHST6 CHSY1 DSE EOGT EXT1 EXT1 EXT2 EXT2 GALNT3 LFNG PAPSS2 PIGA PIGL PIGM PIGN PIGO PIGQ PIGT PIGV PIGW POFUT1 POGLUT1 SLC26A2 SLC35D1 XYLT1

Panel details and technical assay limitations

Clinical information

Gene Disorder name Previous disorder name
Primary panel
ALG1 ALG1-CDG CDG-Ik
ALG2 ALG2-associated myasthenic syndrome CDG-Ii
ALG3 ALG3-CDG CDG-Id
ALG6 ALG6-CDG CDG-Ic
ALG8 ALG8-CDG CDG-Ih
ALG9 ALG9-CDG CDG-IL
ALG11 ALG11-CDG CDG-Ip
ALG12 ALG12-CDG CDG-Ig
ALG13 ALG13-CDG CDG-Is
ATPV0A2 ATP6V0A2-associated cutis laxa NA
B3GLCT B3GLCT-CDG Peters Plus syndrome
CHST14 CHST14-CDG Musculocontractural type Ehlers-Danlos syndrome
COG1 COG1-CDG CDG-IIg
COG2 COG2-CDG NA
COG4 COG4-CDG CDG-IIj
COG5 COG5-CDG CDG-IIi
COG6 COG6-CDG CDG-IIL
COG7 COG7-CDG CDG-IIe
COG8 COG8-CDG CDG-IIh
DOLK DOLK-CDG CDG-Im
DHDDS DHDDS-CDG NA
DPAGT1 DPAGT1-CDG CDG-Ij
DPM1 DPM1-CDG CDG-Ie
DPM2 DPM2-CDG CDG-Iu
DPM3 DPM3-CDG CDG-Io
G6PC3 Congenital neutropenia NA
GFPT1 Congenital myasthenic syndrome NA
GMPPA GMPPA-CDG NA
GMPPB Congenital muscular dystrophy, congenital myasthenic syndrome, and dystroglycanopathy NA
MAGT1 MAGT1-CDG; X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN) syndrome NA
MAN1B1 MAN1B1-CDG NA
MGAT2 MGAT2-CDG CDG-IIa
MOGS MOGS-CDG CDG-IIb
MPDU1 MPDU1-CDG CDG-If
MPI MPI-CDG CDG-Ib
NGLY1 NGLY1-CDG CDG-Iv
PGM1 PGM1-CDG CDG-It
PGM3 PGM3-CDG Hyper-IgE syndrome
PMM2 PMM2-CDG CDG-Ia
RFT1 RFT1-CDG CDG-In
SEC23B SEC23B-CDG Congenital Dyserythropoietic Anemia
SLC35A1 SLC35A1-CDG CDG-IIf
SLC35A2 SLC35A2-CDG CDG-IIm
SLC35C1 SLC35C1-CDG CDG-IIc
SSR4 SSR4-CDG NA
SRD5A3 SRD5A3-CDG CDG-Iq
TMEM165 TMEM165-CDG CDG-IIk
TRIP11 TRIP11-CDG Achondrogenesis type 1A
TUSC3 TUSC3-CDG NA
Preliminary-evidence genes
ALG14 ALG14-CDG Myasthenic syndrome
B4GALT1 B4GALT1-CDG CDG-IId
DDOST DDOST-CDG CDG-Ir
NUS1 NUS1-CDG NA
RPN2 RPN2-CDG NA
SEC23A SEC23A-CDG Cranio-lenticulo-sutural dysplasia
SLC35A3 SLC35A3-CDG NA
ST3GAL3 ST3GAL3-CDG NA
STT3A STT3A-CDG CDG-Iw
STT3B STT3B-CDG CDG-Ix

The congenital disorders of glycosylation (CDGs) are a group of rare disorders that result from a defect in one of the enzymes or transporters involved in the glycosylation of proteins and lipids. Because glycosylation pathways are shared among many proteins and lipids, these disorders often affect multiple organ systems in the body.

Patients with these disorders can have a wide range of symptoms, including developmental delay and intellectual disability, hypotonia, neurological findings (intractable seizures, brain MRI abnormalities such as atrophy and hypoplasia, stroke-like episodes, neuropathy), dysmorphic features (facial, inverted nipples, abnormal fat pads), coagulopathy, and eye abnormalities (optic atrophy, strabismus, retinitis pigmentosa). Some patients may also have features such as gastrointestinal issues, cardiomyopathy, and skeletal dysplasia. Almost any organ system can be affected. Variable expressivity has been observed in many of these disorders, even within families. The vast majority of patients identified to date have presented within the first year of life.

Most patients with defects in either type I or type II N-linked glycosylation will have abnormal patterns on transferrin isoelectric focusing. Patients with some types of O-linked glycosylation may have an abnormal pattern in ApoC-III isoelectric focusing.These assays are not able to determine the individual CDG, however, and some patients with confirmed CDGs have been reported with normal isoelectric focusing studies. Molecular studies are therefore needed to confirm a diagnosis.

The clinical sensitivity for this test is unknown. CDGs are clinically and genetically heterogeneous, and the percentage of patients with a CDG and pathogenic variants in one of the genes offered in this panel has not been determined.

Most CDGs exhibit an autosomal recessive inheritance pattern; however, a small number of CDGs, such as ALG13-CDG (CDG-Is), MGAT1-CDG, SLC35A2-CDG (CDG-IIm), and SSR4-CDG, are inherited in an X-linked manner.

At this time, the prevalence of most individual congenital disorders of glycosylation and the combined prevalence are unknown due to the rarity of these disorders. A prevalence of 1 in 20,000 has been estimated for PMM2-CDG (CDG-Ia), the most common CDG (PMID:11701646).

This test may be considered for individuals with:

  • early-onset multisystem disease
  • patients with abnormal patterns on transferrin or ApoC-III isoelectric focusing

  1. Jaeken, J, Matthijs, G. Congenital disorders of glycosylation. Annu Rev Genomics Hum Genet. 2001; 2:129-51. PMID: 11701646
  2. Foulquier, F. COG defects, birth and rise!. Biochim. Biophys. Acta. 2009; 1792(9):896-902. PMID: 19028570
  3. Xia, B, et al. Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation. Anal. Biochem. 2013; 442(2):178-85. PMID: 23928051
  4. Freeze, HH, et al. Neurological aspects of human glycosylation disorders. Annu. Rev. Neurosci. 2015; 38:105-25. PMID: 25840006
  5. Haeuptle, MA, Hennet, T. Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum. Mutat. 2009; 30(12):1628-41. PMID: 19862844
  6. Freeze, HH, et al. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am. J. Hum. Genet. 2014; 94(2):161-75. PMID: 24507773
  7. Scott, K, et al. Congenital disorders of glycosylation: new defects and still counting. J. Inherit. Metab. Dis. 2014; 37(4):609-17. PMID: 24831587
  8. Sparks, SE, Krasnewich, DM. Congenital Disorders of N-linked Glycosylation Pathway Overview. 2005 Aug 15. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301507

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALG1 NM_019109.4
ALG11 NM_001004127.2
ALG12 NM_024105.3
ALG13 NM_001099922.2
ALG14 NM_144988.3
ALG2 NM_033087.3
ALG3 NM_005787.5
ALG6 NM_013339.3
ALG8 NM_024079.4
ALG9 NM_024740.2
ATP6V0A2 NM_012463.3
B3GALNT2 NM_152490.4
B3GALT6 NM_080605.3
B3GAT3 NM_012200.3
B3GLCT NM_194318.3
B4GALNT1 NM_001478.4
B4GALT1 NM_001497.3
B4GALT7 NM_007255.2
B4GAT1 NM_006876.2
C1GALT1C1 NM_001011551.2
CHST14 NM_130468.3
CHST3 NM_004273.4
CHST6 NM_021615.4
CHSY1 NM_014918.4
COG1 NM_018714.2
COG2 NM_007357.2
COG4 NM_015386.2
COG5 NM_006348.3
COG6 NM_020751.2
COG7 NM_153603.3
COG8 NM_032382.4
DDOST NM_005216.4
DHDDS NM_024887.3
DOLK NM_014908.3
DPAGT1 NM_001382.3
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
DSE NM_013352.3
EOGT NM_173654.2
EXT1 NM_000127.2
EXT1 NM_000127.2
EXT2 NM_207122.1
EXT2 NM_207122.1
FKRP NM_024301.4
FKTN* NM_001079802.1
G6PC3 NM_138387.3
GALNT3 NM_004482.3
GFPT1 NM_001244710.1
GMPPA NM_205847.2
GMPPB NM_013334.3
GNE NM_001128227.2
ISPD NM_001101426.3
LARGE1 NM_004737.4
LFNG NM_001040167.1
MAGT1 NM_032121.5
MAN1B1 NM_016219.4
MGAT2 NM_002408.3
MOGS NM_006302.2
MPDU1 NM_004870.3
MPI NM_002435.2
NGLY1 NM_018297.3
NUS1 NM_138459.3
PAPSS2 NM_001015880.1
PGM1 NM_002633.2
PGM3 NM_001199917.1
PIGA NM_002641.3
PIGL NM_004278.3
PIGM NM_145167.2
PIGN NM_176787.4
PIGO NM_032634.3
PIGQ NM_004204.3
PIGT NM_015937.5
PIGV NM_017837.3
PIGW NM_178517.3
PMM2 NM_000303.2
POFUT1 NM_015352.1
POGLUT1 NM_152305.2
POMGNT1 NM_017739.3
POMGNT2 NM_032806.5
POMK NM_032237.4
POMT1 NM_007171.3
POMT2 NM_013382.5
RFT1 NM_052859.3
RPN2 NM_002951.4
RXYLT1 NM_014254.2
SEC23A NM_006364.3
SEC23B NM_006363.4
SLC26A2* NM_000112.3
SLC35A1 NM_006416.4
SLC35A2 NM_001042498.2
SLC35A3 NM_012243.2
SLC35C1 NM_018389.4
SLC35D1 NM_015139.2
SRD5A3 NM_024592.4
SSR4 NM_001204526.1
ST3GAL3 NM_006279.3
ST3GAL5 NM_003896.3
STT3A NM_001278503.1
STT3B NM_178862.2
TMEM165 NM_018475.4
TRIP11 NM_004239.4
TUSC3 NM_006765.3
XYLT1 NM_022166.3

FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T (also known as NM_001079802.1:c.648-1243G>T) and the ~3 kb retrotransposon insertion in the 3' UTR at position NM_001079802​.1:c.*4392_*4393.
SLC26A2: Analysis includes the intronic variant NM_000112.3:c.-26+2T>C.

Clinical resources
Invitae brochure Metabolic disorders and newborn screening analytes table Metabolic disorders and newborn screening gene list
Patient resources
Patient guide: Genetic testing simplified
Test information
Forms page Specimen requirements page

References

  1. Foulquier, F. COG defects, birth and rise!. Biochim. Biophys. Acta. 2009; 1792(9):896-902. PMID: 19028570
  2. Freeze, HH, et al. Neurological aspects of human glycosylation disorders. Annu. Rev. Neurosci. 2015; 38:105-25. PMID: 25840006
  3. Freeze, HH, et al. Solving glycosylation disorders: fundamental approaches reveal complicated pathways. Am. J. Hum. Genet. 2014; 94(2):161-75. PMID: 24507773
  4. Haeuptle, MA, Hennet, T. Congenital disorders of glycosylation: an update on defects affecting the biosynthesis of dolichol-linked oligosaccharides. Hum. Mutat. 2009; 30(12):1628-41. PMID: 19862844
  5. Jaeken, J, Matthijs, G. Congenital disorders of glycosylation. Annu Rev Genomics Hum Genet. 2001; 2:129-51. PMID: 11701646
  6. Scott, K, et al. Congenital disorders of glycosylation: new defects and still counting. J. Inherit. Metab. Dis. 2014; 37(4):609-17. PMID: 24831587
  7. Sparks, SE, Krasnewich, DM. Congenital Disorders of N-linked Glycosylation Pathway Overview. 2005 Aug 15. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301507
  8. Xia, B, et al. Serum N-glycan and O-glycan analysis by mass spectrometry for diagnosis of congenital disorders of glycosylation. Anal. Biochem. 2013; 442(2):178-85. PMID: 23928051

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