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Familial Limb Girdle Myasthenic Syndrome With Tubular Aggregates via the DPAGT1 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
11259 DPAGT1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11259DPAGT181479 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 post synaptic proteins. Clinically, a limb-girdle pattern of muscle involvement makes DOK7, AGRN, GFPT1, and DPAGT1-related CMS unique from other CMS. Belaya et al. (Am J Hum Genet 91:193-201, 2012) found mutations in the DPAGT1 gene (OMIM 191350) in four families with autosomal recessive limb-girdle myasthenic syndrome with tubular aggregates. Age of onset ranged from 6 month to 7 years of life. Presenting symptoms included proximal weakness; hypotonia and poor head control; difficulty walking; abnormal gait; and delayed motor development. Ptosis and ophthalmoplegia were documented in one of the five and none of five patients, respectively, among the four families. Scoliosis was present in 2/5 patients. Repetitive nerve stimulation revealed a decremental response in all five patients, and single-fiber EMG showed abnormal jitter and blocking. Tubular aggregates were seen in 4/4 muscle biopsies. Clinical symptoms were either stable or slowly progressive in all patients. All five affected subjects responded to acetylcholinesterase inhibitors and two patients showed improvement by taking 3,4-diaminopyridine, a drug which increases acetylcholine release from the nerve terminal. Patients with other forms of limb-girdle myasthenic syndrome with tubular aggregates also respond well to treatment with acetylcholinesterase inhibitors (Rodolico et al. Neuromusc Disord 12:964-969, 2002; Beeson et al. Science 313: 1975-1978, 2006).

Genetics

Abnormalities of proteins involved with neuromuscular transmission underlie familial limb-girdle myasthenic syndrome, congenital myasthenic 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. DPAGT1 encodes an enzyme that catalyzes the first committed step of N-linked protein glycosylation. Beyala et al. (2012) showed that DPAGT1 enzyme activity is required for efficient glycosylation of acetylcholine-receptor subunits and for efficient export of acetylcholine receptors to the cell surface. Familial limb-girdle myasthenic syndrome with tubular aggregates due to DPAGT1 mutations is inherited as an autosomal recessive disorder (Belaya et al. 2012). Among the initial cohort of DPAGT1-related familial limb-girdle myasthenic syndrome patients, five missense and one single base deletion causative mutation were described (Bayala et al. 2012).

Acyl-CoA:diacylglycerol acyltransferase is encoded by exons 1–9 of the DPAGT1 gene.

Clinical Sensitivity - Sequencing with CNV PGxome

DOK7, AGRN, GFPT1, and DPAGT1 mutations 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 DPAGT1 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 slowly progressive or stable limb-girdle pattern of muscle weakness without facial involvement and tubular aggregates in muscle. Limb-girdle CMS patients who respond to AChE inhibitors. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DPAGT1.

Gene

Official Gene Symbol OMIM ID
DPAGT1 191350
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Beeson, D., et.al. (2006). "Dok-7 mutations underlie a neuromuscular junction synaptopathy." Science 313(5795): 1975-8. PubMed ID: 16917026
  • Belaya et al. "Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates". Am J Hum Genet 91: 193-201, 2012. PubMed ID: 22742743
  • Rodolico et al. "Limb-girdle myasthenia: clinical, electrophysiological and morphological features in familial and autoimmune cases". Neuromusc Disord 12: 964-969, 2002.  PubMed ID: 12467753

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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