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Congenital Myasthenic Syndrome 24 via the MYO9A 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
13333 MYO9A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13333MYO9A81479 81479,81479 $890 Order Options and Pricing

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).

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 abnormalities of presynaptic, synaptic, or post synaptic proteins. CMS are characterized by fatigable weakness affecting limb, ocular, facial, and bulbar muscles. Neonates present with feeding problems, choking, feeble cry, and muscle weakness (Vanhaesebrouck and Beeson. 2019. PubMed ID: 31361628; Abicht et al. 2016. PubMed ID: 20301347). Some neuromuscular junction genes can result in a more severe presentation of fetal akinesia, intrauterine growth retardation, arthrogryposis, lung hypoplasia, cleft palate, and cryptorchidism (Pergande et al. 2020. PubMed ID: 31680123). Patients presenting in later childhood are seen with abnormal exercise-induced fatigue and difficulty running. Most patients present prior to 2 years of age, although rare exceptions have been reported (Vanhaesebrouck and Beeson. 2019. PubMed ID: 31361628; Abicht et al. 2016. PubMed ID: 20301347). Symptoms are extremely variable, and are in some case induced by febrile illness, infection, or excitement. Life threatening respiratory crises may occur in affected neonates or older children. CMS may be differentiated from myasthenia gravis, an acquired autoimmune disorder, by earlier age at onset and by negative serology tests for anti-acetylcholine receptor (AchR) and anti-Musk antibodies.

Congenital myasthenic syndrome 24 or related disorders have been described in at least five individuals from four different families. Three individuals presented with classic features of CMS including ptosis, respiratory failure, hypotonia, proximal and distal muscle weakness, and difficulty swallowing and chewing (O'Connor et al. 2016. PubMed ID: 27259756). An additional individual with compound heterozygous variants presented with distal arthrogryposis, contractures of knees, camptodactylyl, and talipes equinovarus (Bayram et al. 2016. PubMed ID: 26752647). A patient homozygous for a nonsense variant presented with more severe features of hydrocephalus and fetal akinesia (Maddirevula et al. 2018. PubMed ID: 30237576). Genetic testing may aid in establishing a differential diagnosis and may assist reproductive planning.

Genetics

Pathogenic variants in the MYO9A gene are associated with autosomal recessive congenital myasthenic syndrome 24. Missense variants and one nonsense variant have been reported to date and have been inherited from a carrier parent. No structural variants have been reported.

The MYO9A gene encodes an unconventional myosin protein which is part of a family of molecular motors. MYO9A appears to be of particular importance in neuronal branching and axon guidance and appears to be required for formation of the neuromuscular junction during development (O'Connor et al. 2016. PubMed ID: 27259756). Knockdown of MYO9A in zebrafish resulted in abnormal movement and tail curvature (O'Connor et al. 2016. PubMed ID: 27259756). MYO9A has been cited as a nonessential gene for growth of human tissue culture cells (Online Gene Essentiality). MYO9A is relatively intolerant to loss-of-function variants (gnomAD).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity is difficult to estimate, as to date, a limited number of cases have been described in the literature. Analytical sensitivity should be high as all pathogenic variants reported to date are detectable by sequencing.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the MYO9A gene plus 10 bases flanking noncoding DNA in all available transcripts in addition to 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

Candidates for this test are patients with clinical features of congenital myasthenic syndrome or fetal akinesia. Targeted testing is indicated for family members of patients who have known pathogenic variants in MYO9A. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in MYO9A.

Gene

Official Gene Symbol OMIM ID
MYO9A 604875
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Myasthenic syndrome, congenital, 24, presynaptic AR 618198

Citations

  • Abicht et al. 2016. PubMed ID: 20301347
  • Bayram et al. 2016. PubMed ID: 26752647
  • Genome Aggregation Database.
  • Maddirevula et al. 2018. PubMed ID: 30237576
  • O'Connor et al. 2016. PubMed ID: 27259756
  • Online Gene Essentiality (OGEE).
  • Pergande et al. 2020. PubMed ID: 31680123
  • Vanhaesebrouck and Beeson. 2019. PubMed ID: 31361628

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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