Congenital Disorders of Glycosylation, Type Ih (CDG Ih) via the ALG8 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9923 ALG8 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9923ALG881479 81479(x2) $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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 (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. Consequently, the majority of these disorders demonstrate multi-system involvement. 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).

CDG type Ih, an N-linked glycosylation defect, has been described in approximately 20 individuals to date (Höck et al. 2015. PubMed ID: 26066342; Bastaki et al. 2018. PubMed ID: 28940310). Patients generally present at birth or during the neonatal period, and disease progression is often rapid. Symptoms include dysmorphic features, which are characterized by retrognathia, low-set ears, hypertelorism, and/or pes equinovarus; muscular hypotonia; hepatomegaly; coagulopathy, often notably thrombocytopenia; edema and ascites, which may include fetal hydrops; cardiorespiratory problems; gastrointestinal signs including diarrhea, vomiting, feeding problems, and protein-losing enteropathy; and occasionally congenital cataracts (Höck et al. 2015. PubMed ID; 26066342). Patients often show signs of brain involvement, such as psychomotor delays, seizures, ataxia, and/or structural abnormalities. Additionally, affected individuals may also display fat pads, wrinkly skin, cutis laxa, and/or inverted nipples. Plasma isoelectric focusing of transferrin of these patients demonstrates a type I pattern (CDG-I).

Genetics

Congenital disorder of glycosylation type Ih is inherited in an autosomal recessive manner. The ALG8 gene encodes a protein (dolichyl-phosphate-glucose 1-mannose 9-N-acetylglucosamine glucosyltransferase) required for the addition of the second glucose residue onto lipid-linked oligosaccharides (Chantret et al. 2003. PubMed ID: 12480927). The majority of causative variants reported in this gene to date are missense; however, one nonsense, three splicing, three small frameshift deletions, and one single basepair duplication have also been reported (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Due to the low incidence of this disorder clinical sensitivity cannot be precisely estimated. However, all coding and non-coding regions of the ALG8 gene that harbor causative variants reported in the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/) as of 06/20/2019 are covered in this test.

Testing Strategy

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV-calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.

This test provides full coverage of all coding exons of the ALG8 gene 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 full coverage as >20X NGS reads or Sanger sequencing.

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test include individuals with clinical symptoms consistent with CDG Ih or patients with demonstrated dolichyl-phosphate-glucose 1-mannose 9-N-acetylglucosamine glucosyltransferase deficiency (and/or accumulation of the enzymatic substrate). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ALG8.

Gene

Official Gene Symbol OMIM ID
ALG8 608103
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Congenital Disorder Of Glycosylation Type 1H AR 608104

Citations

  • Bastaki et al. 2018. PubMed ID: 28940310
  • Brasil et al. 2018. PubMed ID: 29702557
  • Chantret et al. 2003. PubMed ID: 12480927
  • Höck et al. 2015. PubMed ID: 26066342
  • Human Gene Mutation Database (Biobase).
  • Jaeken. 2017. PubMed ID: 28484880
  • Scott et al. 2014. PubMed ID: 24831587

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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
×