Test Code: 8451

Congenital Disorder of Glycosylation, GNE-related: GNE Gene Sequencing
Test Code: 8451
Turnaround time: 7 weeks


Congenital disorders of glycosylation (CDG) are a group of autosomal recessive genetic disorders caused by the alteration in synthesis and structure of protein and lipid glycosylation. In the past decade, over 30 genetic diseases have been identified that alter glycan synthesis, structure and ultimately the function of nearly all organ systems.

CDG type I (CDGI) disorders result from impaired synthesis of the incomplete lipid linked oligosaccharide (LLO) and/or its attachment to the growing polypeptide chain. CDG-Ia is the most common form reported, due to phosphomannomutase deficiency, an enzyme that converts mannose-6-phosphate to mannose-1-phosphate. CDG-Ib (phosphomannose isomerase, MPI deficiency) is the only known treatable form, by giving mannose orally. CDG type II (CDGII) includes defects in processing of N-glycans.

Phenotypes of this disorder are extremely variable. Manifestations range from severe developmental delay and hypotonia with multiple organ system involvement beginning in infancy, to hypoglycemia and protein-losing enteropathy with normal development. Most subtypes have been described in only a few individuals, however, thus understanding of the phenotypes is limited.

The current diagnostic test for CDG is analysis of serum transferrin glycoforms, also called “transferrin isoforms analysis”, or “carbohydrate-deficient transferrin analysis.” If positive, this testing can be followed by DNA testing to identify mutations in the gene involved.

Sialic acid modification of glycoproteins and glycolipids expressed at the cell surface is crucial for their function in many biologic processes, including cell adhesion and signal transduction. Differential sialylation of cell surface molecules is also implicated in the tumorigenicity and metastatic behavior of malignant cells. GNE is the rate-limiting enzyme in the sialic acid biosynthetic pathway.

Mutations in the GNE gene (9p12-p11) have been identified in individuals with sialuria (autosomal dominant inheritance), autosomal recessive inclusion body myopathy, and Nonaka myopathy (autosomal recessive inheritance).

For patients with suspected GNE-related CDG, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.

• Freeze HH. Congenital disorders of glycosylation: CDG-I, CDG-II, and beyond. Curr Mol Med 2007; 7:389-396.
• GeneTests: Congenital Disorders of Glycosylation Overview
• Jaeken J, Matthijs G. Congenital disorders of glycosylation: A rapidly expanding disease family. Annu Rev Genomics Hum Genet 2007;8:261- 278.
• OMIM: UDP-N-Acetylglucosamine 2-Epimerase/N-Acetylmannosamine kinase


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of GNE-related CDG
  • Carrier testing in adults with a family history of GNE-related CDG


PCR amplification of 13 exons contained in the GNE gene is performed on the patient’s genomic DNA. Direct sequencing of amplification products is performed in both forward and reverse directions, using automated fluorescence dideoxy sequencing methods. The patient’s gene sequences are then compared to a normal reference sequence. Sequence variations are classified as mutations, benign variants unrelated to disease, or variations of unknown clinical significance. Variants of unknown clinical significance may require further studies of the patient and/or family members. This assay does not interrogate the promoter region, deep intronic regions, or other regulatory elements, and does not detect large deletions.


Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s biochemical phenotype.

Analytical Sensitivity: ~99%


Submit only 1 of the following specimen types
* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Submit copies of diagnostic biochemical test results with the sample, if appropriate.
Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed by another third party provider, please submit a copy of the sequencing report with the test requisition.

• Deletion/duplication analysis of the GNE gene by CGH array is available for those individuals in whom sequence analysis is negative.
• Analysis of other CDG genes is also available.
• Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.