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GM2-Gangliosidosis Variant AB via the GM2A Gene

Order Options and Pricing
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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
GM2A 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9231GM2A81479 81479,81479 $990 Order Options and Pricing

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Jana Paderova, PhD

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 platform).

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

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

  • Jana Paderova, PhD

Clinical Features and Genetics

Indications for Test

This test is indicated for patients with symptoms similar to that of Tay-Sachs disease in spite of normal levels of beta-hexosaminidase A and B isoenzymes; and family members of patients with known pathogenic variants in the GM2A gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GM2A.

Clinical Features

GM2-Gangliosidosis variant AB, also known as Tay-Sachs disease AB Variant, is the rarest form of GM2-gangliosidoses. It is due to deficiency of the GM2 activator protein. Only six cases, confirmed by molecular genetic analysis, have been reported in the literature. They all presented with the acute form of GM2 gangliosidosis, which is clinically undistinguishable from the classical acute forms of Tay-Sachs and Sandhoff phenotypes (Gravel 2001). Symptoms begin in infancy and include psychomotor retardation, motor weakness, hypotonia, hyporeflexia, infantile spasms, motor seizures, myoclonic jerks, exaggerated startle response, macular cherry-red spots, visual abnormalities, and impaired sucking and swallowing. Disease progression is rapid and associated with nystagmus, hepatomegaly and brain atrophy (Schröder et al. 1991; Schröder et al. 1993; Schepers et al. 1996; Chen et al. 1999; Kolodny, 2008).

Genetics

GM2-Gangliosidosis variant AB is inherited in an autosomal recessive manner and results from pathogenic variants in the GM2A gene (Schröder et al. 1991). A total of six causative variants have been detected and include three missense, one nonsense, and two small deletions. They were reported in patients from various ethnic and geographic origins, including Saudi Arabian and Spanish from consanguineous families (Schepers et al. 1996) ; and African-American (Schröder et al. 1991)  and Laotian-Hmong (Chen et al. 1999) with no apparent history of consanguinity. 

The GM2A gene encodes the GM2 activator protein, a binding protein required for the hydrolysis of GM2 gangliosides by the beta-hexosaminidase A.  It forms a complex with GM2 ganglioside, which interacts specifically with beta-hexosaminidase A in the lysosomes (Gravel et al. 2002).

Clinical Sensitivity - Sequencing with CNV PGxome

Pathogenic variants in the GM2A gene appear to be a rare cause of GM2 gangliosidoses.

To date, no pathogenic large deletions or duplications in the GM2A gene have been reported (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the GM2A 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

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

This test is indicated for patients with symptoms similar to that of Tay-Sachs disease in spite of normal levels of beta-hexosaminidase A and B isoenzymes; and family members of patients with known pathogenic variants in the GM2A gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GM2A.

Gene

Official Gene Symbol OMIM ID
GM2A 613109
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Tay-Sachs disease AB Variant AR 272750

Related Test

Name
Sandhoff Disease via the HEXB Gene

Citations

  • Chen B, Rigat B, Curry C, Mahuran DJ.  1999.  Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet 65:77-87. PubMed ID: 10364519
  • Chen B, Rigat B, Curry C, Mahuran DJ.  1999.  Structure of the GM2A gene: identification of an exon 2 nonsense mutation and a naturally occurring transcript with an in-frame deletion of exon 2. Am J Hum Genet 65:77-87. PubMed ID: 10364519
  • Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K and Suzuki K. 2001. The GM2 Gangliosidoses.  In: Scriver et al. Eds 8 Vol 3 McGraw-Hill, New York, 3827-3877.
  • Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K and Suzuki K. 2001. The GM2 Gangliosidoses.  In: Scriver et al. Eds 8 Vol 3 McGraw-Hill, New York, 3827-3877.
  • Human Gene Mutation Database (Bio-base).
  • Kolodny. 2008. Mol Genet Metab 93 S27.  Poster.
  • Schepers U, Glombitza G, Lemm T, Hoffmann A, Chabas A, Ozand P, Sandhoff K. 1996. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet 59:1048-1056. PubMed ID: 8900233
  • Schepers U, Glombitza G, Lemm T, Hoffmann A, Chabas A, Ozand P, Sandhoff K. 1996. Molecular analysis of a GM2-activator deficiency in two patients with GM2-gangliosidosis AB variant. Am J Hum Genet 59:1048-1056. PubMed ID: 8900233
  • Schröder M, Schnabel D, Hurwitz R, Young E, Suzuki K, Sandhoff K. 1993. Molecular genetics of GM2-gangliosidosis AB variant: a novel mutation and expression in BHK cells. Hum Genet 92:437-440. PubMed ID: 8244332
  • Schröder M, Schnabel D, Suzuki K, Sandhoff K. 1991. A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB. FEBS Lett 290:1-3. PubMed ID: 1915858
  • Schröder M, Schnabel D, Suzuki K, Sandhoff K. 1991. A mutation in the gene of a glycolipid-binding protein (GM2 activator) that causes GM2-gangliosidosis variant AB. FEBS Lett 290:1-3. PubMed ID: 1915858

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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