GYG1-Related Disorders via the GYG1 Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
3364 GYG1$750.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Clinical sensitivity of this test is expected to be high as, to date, all identified patients have been found to have two pathogenic variants detectable via direct sequencing, suggesting a clinical sensitivity near 100% (Moslemi et al. 2010; Malfatti et al. 2014; Fanin et al. 2015; Akman et al. 2016).

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Clinical Features

Glycogen Storage Disease Type XV (GSD XV) and Polyglucosan Body Myopathy Type 2 (PGBM2) are rare, allelic disorders caused by a deficiency of the glycogenin-1 protein, which is encoded by the GYG1 gene. To date, only one individual has been reported with GSD XV (Moslemi et al. 2010). This patient presented in the third decade of life with cardiomyopathy and muscle weakness associated with a profound depletion of glycogen in skeletal muscle. There was some suspicion that the onset of the myopathic features may have been in childhood.

More commonly, variants in the GYG1 gene have been reported to be associated with PGBM2. These patients present with muscle weakness without cardiomyopathy. The age of onset and severity are variable, although the myopathy has been reported to be progressive in nearly all patients. Serum creatine kinase (CK) levels have been reported to be slightly elevated in some patients. In all PGBM2 patients, partially amylase-resistant periodic acid-Schiff (PAS)-positive inclusions have been detected in a portion of muscle fibers, with normal glycogen detected in the remaining fibers. In many of the patients, the inclusions have been confirmed via electron microscopy to be polyglucosan bodies (Malfatti et al. 2014; Fanin et al. 2015; Akman et al. 2016). Polyglucosan bodies are accumulations or abnormally structured glycogen that are poorly branched and may be less spherical than normal glycogen granules.


Both GSD Type XV and PGBM2 are autosomal recessive disorders. Pathogenic variants in the GYG1 gene are the only known cause of both of these disorders. To date, nearly 10 different causative variants have been reported in a total of 16 patients. The most commonly reported variant is defined as c.143+3G>C, which has been shown to result in the skipping of exon 2 (Malfatti et al. 2014). This variant has been reported in the homozygous or compound heterozygous state in approximately two-thirds of patients. The remaining variants appear to be private, and include missense, nonsense, frameshift and other splice variants, and are spread throughout the gene (Human Gene Mutation Database).  

The GYG1 gene encodes the protein glycogenin-1, which is necessary for the initiation of glycogen synthesis in muscle tissues. Autoglucosylation of glycogenin results in the formation of a short primer for glycogen synthesis, containing approximately 10 glucose residues. After the primer is generated, glycogen elongation and branching is catalyzed by glycogen synthase and glycogen branching enzyme (Moslemi et al. 2010; Chen et al. 2014).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the GYG1 gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results. 

Indications for Test

Patients with clinical features of GSD XV or PGBM2 are candidates for this test, particularly if amylase-resistant PAS-positive inclusions suggestive of polyglucosan bodies have been identified on a muscle biopsy. Family members of patients known to have GYG1 variants are also good candidates, and we will also sequence the GYG1 gene to determine carrier status.


Official Gene Symbol OMIM ID
GYG1 603942
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Glycogen Storage Disease and Disorders of Glucose Metabolism Sequencing Panel


Genetic Counselors
  • Akman H.O. et al. 2016. Neuromuscular Disorders : Nmd. 26: 16-20. PubMed ID: 26652229
  • Chen Y., Kishnani P.S. and Koeberl D. 2014. Glycogen Storage Diseases. In: Valle D, Beaudet AL, Vogelstein B, et al., editors. New York, NY: McGraw-Hill. OMMBID.
  • Fanin M. et al. 2015. Neurology. Genetics. 1: e21. PubMed ID: 27066558
  • Human Gene Mutation Database (Bio-base).
  • Malfatti E. et al. 2014. Annals of Neurology. 76: 891-8. PubMed ID: 25272951
  • Moslemi A.R. et al. 2010. The New England Journal of Medicine. 362: 1203-10. PubMed ID: 20357282
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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