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Familial Limb Girdle Myasthenic Syndrome via the AGRN 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
11077 AGRN 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11077AGRN81479 81479,81479 $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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Congenital myasthenic syndromes (CMS) are disorders of the neuromuscular junction resulting from defects in presynaptic, synaptic, or postsynaptic proteins. Agrin is produced by the presynaptic neuron and released into the synaptic space and functions by activating MuSK. Clinically, a limb girdle pattern of muscle involvement makes DOK7 and AGRN-related CMS unique from other CMS. Age of onset typically ranges from birth to five years of age (Selcen et al. Ann Neurol 64:71-78, 2008; Beeson et al. Science 313:1975-1978, 2006). Thus far, one family has been reported with AGRN-associated familial limb girdle myasthenic syndrome (Huzé et al. Am J Hum Genet 85:155-167, 2009). The affected siblings reported having difficulty running beginning in childhood, mild facial weakness, unilateral ptosis, and thin thorax and pelvis. In adulthood, muscle function was stable although weakness worsened in one sibling during pregnancy and menstruation. Disorganization of the neuromuscular junction was evident in a muscle biopsy from an affected individual. Treatment with ephedrine was found to cause sustained improvement in muscle performance and endurance.

Genetics

Abnormalities of proteins involved with neuromuscular transmission underlie familial limb girdle myasthenia syndrome, congenital myasthenia syndromes, Pena-Shokeir syndrome, and multiple pterygium syndromes. These disorders, which may represent a phenotypic continuum of a single entity, are most often inherited in an autosomal recessive manner. Familial limb girdle myasthenic syndrome due to AGRN (OMIM 103320) variants is inherited as an autosomal recessive disorder. Affected members of the family with AGRN-associated CMS were homozygous for a c.5125G>C (p.Gly1709Arg) variant (Huzé et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

DOK7, AGRN, and GFPT1 variants are the only known cause of familial limb-girdle myasthenic syndrome. Clinical sensitivity should be high for patients meeting rigorous clinical, histopathological, and electrophysiological criteria.

Testing Strategy

This test provides full coverage of all coding exons of the AGRN 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

Patients with a limb girdle pattern of muscle weakness and other typical CMS muscle involvement. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in AGRN.

Gene

Official Gene Symbol OMIM ID
AGRN 103320
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Myasthenia, Limb-Girdle, Familial AR 254300

Citations

  • Beeson, D., et.al. (2006). "Dok-7 mutations underlie a neuromuscular junction synaptopathy." Science 313(5795): 1975-8. PubMed ID: 16917026
  • Huze, C., et.al. (2009). "Identification of an agrin mutation that causes congenital myasthenia and affects synapse function." Am J Hum Genet 85(2): 155-67. PubMed ID: 19631309
  • Selcen, D., et.al. (2008). "Dok-7 myasthenia: phenotypic and molecular genetic studies in 16 patients." Ann Neurol 64(1): 71-87. PubMed ID: 18626973

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

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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: $
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