Invitae Congenital Disorders of Glycosylation Panel

Ordering
  • 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
  • Sample requirements
  • Request a sample kit
Billing

Test description

The Invitae Congenital Disorders of Glycosylation Panel analyzes up to 54 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)

Order test

Primary panel (36 genes)

ALG1 ALG11 ALG12 ALG13 ALG2 ALG3 ALG6 ALG8 ALG9 ATP6V0A2 B3GLCT CHST14 COG1 COG4 COG5 COG6 COG7 COG8 DOLK DPAGT1 DPM1 DPM2 DPM3 MGAT2 MOGS MPDU1 MPI NGLY1 PGM1 PMM2 RFT1 SLC35A1 SLC35A2 SLC35C1 SRD5A3 TMEM165

Add-on preliminary-evidence genes (3 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.

DDOST STT3A STT3B

Add-on disorders of O-mannosylation genes (15 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 GFPT1 GMPPB GNE ISPD LARGE POMGNT1 POMGNT2 POMK POMT1 POMT2 TMEM5

FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.

Disorder name Previous disorder name
Primary panel
ALG1-CDG CDG-Ik
ALG2-associated myasthenic syndrome CDG-Ii
ALG3-CDG CDG-Id
ALG6-CDG CDG-Ic
ALG8-CDG CDG-Ih
ALG9-CDG CDG-IL
ALG11-CDG CDG-Ip
ALG12-CDG CDG-Ig
ALG13-CDG CDG-Is
ATP6V0A2-associated cutis laxa
B3GLCT-CDG Peters Plus syndrome
CHST14-CDG Musculocontractural type Ehlers-Danlos syndrome
COG1-CDG CDG-IIg
COG4-CDG CDG-IIj
COG5-CDG CDG-IIi
COG6-CDG CDG-IIL
COG7-CDG CDG-IIe
COG8-CDG CDG-IIh
DOLK-CDG CDG-Im
DPAGT1-CDG CDG-Ij
DPM1-CDG CDG-Ie
DPM2-CDG CDG-Iu
DPM3-CDG CDG-Io
MGAT2-CDG CDG-IIa
MOGS-CDG CDG-IIb
MPDU1-CDG CDG-If
MPI-CDG CDG-Ib
NGLY1-CDG CDG-Iv
PGM1-CDG CDG-It
PMM2-CDG CDG-Ia
RFT1-CDG CDG-In
SLC35A1-CDG CDG-IIf
SLC35A2-CDG CDG-IIm
SLC35C1-CDG CDG-IIc
SRD5A3-CDG CDG-Iq
TMEM165-CDG CDG-IIk
Preliminary-evidence genes
DDOST-CDG CDG-Ir
STT3A-CDG CDG-Iw
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) and SLC35A2-CDG (CDG-IIm), 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

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALG1 NM_019109.4
ALG11 NM_001004127.2
ALG12 NM_024105.3
ALG13 NM_001257230.1
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
B3GLCT NM_194318.3
B4GAT1 NM_006876.2
CHST14 NM_130468.3
COG1 NM_018714.2
COG4 NM_015386.2
COG5 NM_006348.3
COG6 NM_020751.2
COG7 NM_153603.3
COG8 NM_032382.4
DDOST NM_005216.4
DOLK NM_014908.3
DPAGT1 NM_001382.3
DPM1 NM_003859.1
DPM2 NM_003863.3
DPM3 NM_153741.1
FKRP NM_024301.4
FKTN* NM_001079802.1
GFPT1 NM_002056.3
GMPPB NM_021971.2
GNE NM_001128227.2
ISPD NM_001101426.3
LARGE NM_004737.4
MGAT2 NM_002408.3
MOGS NM_006302.2
MPDU1 NM_004870.3
MPI NM_002435.2
NGLY1 NM_018297.3
PGM1 NM_002633.2
PMM2 NM_000303.2
POMGNT1 NM_017739.3
POMGNT2 NM_032806.5
POMK NM_032237.4
POMT1 NM_007171.3
POMT2 NM_013382.5
RFT1 NM_052859.3
SLC35A1 NM_006416.4
SLC35A2 NM_001042498.2
SLC35C1 NM_018389.4
SRD5A3 NM_024592.4
STT3A NM_001278503.1
STT3B NM_178862.2
TMEM165 NM_018475.4
TMEM5 NM_014254.2

FKTN: Analysis includes the intronic variant NM_001079802.1:c.647+2084G>T as well as the 3 kb retrotransposon insertion in the 3' UTR at c.*4287_*4288ins3062.