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Familial Limb Girdle Myasthenia Syndrome via the DOK7 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7629 DOK7 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7629DOK781479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

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. The protein encoded by DOK7 is essential for neuromuscular synaptogenesis due to its role in inducing autophosphorylation of the skeletal muscle receptor-like tyrosine kinase (MuSK), a key protein involved in postsynaptic differentiation (Okada et al. Science 312:1802-1805, 2006). Variants in DOK7 result in small neuromuscular junctions but normal acetylcholine receptor and acetylcholinesterase function (Beeson et al. Science 313:1975-1978, 2006). Electron microscopy studies of patients with DOK7 variants shows destruction and remodeling of end plates at neuromuscular junctions (Selcen et al. Ann Neurol 64:71-87, 2008). Clinically, a limb girdle pattern of muscle involvement makes DOK7-related CMS unique from other forms of CMS. Age at onset typically ranges from birth to five years of age (Selcen et al. 2008) with onset in a minority of patients occurring beyond age five years (Beeson et al. 2006). The latter study found that the most common clinical presentation was difficulty in walking after initially achieving normal walking milestones. In a cohort of sixteen DOK7 positive patients characterized by Selcen et al. (2008), disease severity and rate of progression was variable; some patients exhibited mild static weakness limited to limb girdle muscles, while others had severe generalized disease with muscle atrophy. Ten of the sixteen patients had intermittent worsening of symptoms lasting from days to weeks. All patients reported fatigue on exertion and proximal muscle weakness. Other common features among the sixteen patients included ptosis (14/16), facial weakness (13/16), bulbar symptoms (11/16), and respiratory difficulties (13/16).

Genetics

Familial limb girdle myasthenic syndrome due to DOK7 gene variants (OMIM 254300) is inherited as an autosomal recessive disorder. In a cohort of 21 patients, Beeson et al. (2006) found 16 to have the same exon 7  variant (c.1124_1127dupTGCC). Fourteen of 16 patients reported by Selcen et al. (2008) had a least one allele with the c.1124_1127dupTGCC variant, and four were found to have heterozygous gross alterations (intron inclusion or exon skipping) undetectable in genomic DNA.

Clinical Sensitivity - Sequencing with CNV PG-Select

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 DOK7 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Individuals with a limb girdle pattern of muscle weakness along with other typical CMS muscle involvement. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DOK7.

Gene

Official Gene Symbol OMIM ID
DOK7 610285
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Fetal Akinesia Deformation Sequence (FADS)/Lethal Multiple Pterygium Syndrome Panel

Citations

  • Beeson, D., et.al. (2006). "Dok-7 mutations underlie a neuromuscular junction synaptopathy." Science 313(5795): 1975-8. PubMed ID: 16917026
  • Okada, K., et.al. (2006). "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis." Science 312(5781): 1802-5. PubMed ID: 16794080
  • 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

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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.
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