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Congenital Myasthenic Syndrome via the CHRNE 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
6995 CHRNE 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
6995CHRNE81479 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 abnormalities of presynaptic, synaptic, or postsynaptic 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. 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 are reported (eg. Croxen et al. Neurol 59:162-168, 2002). Symptoms are extremely variable and are in some cases induced by febrile illness, infection, or excitement (eg. Byring et al. Neuromuscul Disord 12:548-553, 2002). 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 of onset and by negative serology tests for anti-acetylcholine receptor (AchR) and anti-Musk antibodies. CHRNE gene variants have been found in patients with fast and slow channel CMS as well as in patients with severe end-plate acetylcholine receptor deficiency (Engel and Sine. Curr Opinion in Pharmacol 5:308-321, 2005).

Genetics

Abnormalities of proteins involved with neuromuscular transmission underlie congenital myasthenic syndromes (CMS), limb girdle CMS, 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. Fast channel CMS (OMIM 608930) secondary to loss-of-function variants in the acetylcholine receptor epsilon gene (CHRNE, OMIM 100725) is inherited as a recessive condition (Ohno et al. Neuron 17:157-170, 1996; Ohno et al. Hum Mol Genet 6:753-766, 1997; Ohno et al. Ann Neurol 44:234-241, 1998). Slow-channel CMS (OMIM #601462) secondary to gain-of-function variants in the CHRNE gene is mostly inherited as a dominant condition (Engel et al. Hum Mol Genet 5:1217-1227, 1996), although recessive inheritance has also been reported (Croxen et al. 2002). CMS with end-plate AChR deficiency is inherited as a recessive condition and is the most common form of CMS. CHRNE variants that result in reduced expression of the epsilon subunit are the most common cause of CMS with end-plate AChR deficiency. Such variants result in termination codons (Engel et al. Ann Neurol 40:810-817, 1996), defective splicing (Ohno et al. 1998), or compromised gene regulation (Abicht et al. Brain 125:1005-1013, 2005; Ohno et al. Neuromusc Disord 9:131-135, 1999; Ohno et al. 1996).

The epsilon subunit of the acetylcholine receptor is encoded by exons 1 – 12 of the CHRNE gene located on chr 17p13.

Clinical Sensitivity - Sequencing with CNV PG-Select

Sensitivity for CMS testing is at least 50% overall; 30% for CHRNE, 10% for RAPSN, and 7.5% for COLQ (GeneReviews, Abicht and Lochmüller, 2006).

Testing Strategy

This test provides full coverage of all coding exons of the CHRNE gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

A comprehensive diagnostic algorithm can be found in (GeneReviews, Abicht and Lochmüller, 2006). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CHRNE.

Gene

Official Gene Symbol OMIM ID
CHRNE 100725
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

  • Abicht, A., et.al. (2002). "A newly identified chromosomal microdeletion and an N-box mutation of the AChR epsilon gene cause a congenital myasthenic syndrome." Brain 125(Pt 5): 1005-13. PubMed ID: 11960891
  • Angela Abicht, Hanns Lochmuller (2006). "Congenital Myasthenic Syndromes."
  • Byring RF, Pihko H, Tsujino A, Shen XM, Gustafsson B, Hackman P, Ohno K, Engel AG, Udd B. 2002. Congenital myasthenic syndrome associated with episodic apnea and sudden infant death. Neuromuscul Disord 12: 548-553. PubMed ID: 12117478
  • Croxen R, Hatton C, Shelley C, Brydson M, Chauplannaz G, Oosterhuis H, Vincent A, Newsom-Davis J, Colquhoun D, Beeson D. 2002. Recessive inheritance and variable penetrance of slow-channel congenital myasthenic syndromes. Neurology 59: 162-168. PubMed ID: 12141316
  • Engel, A. G., et.al. (1996). "End-plate acetylcholine receptor deficiency due to nonsense mutations in the epsilon subunit." Ann Neurol 40(5): 810-7. PubMed ID: 8957026
  • Engel, A. G., et.al. (1996). "New mutations in acetylcholine receptor subunit genes reveal heterogeneity in the slow-channel congenital myasthenic syndrome." Hum Mol Genet 5(9): 1217-27. PubMed ID: 8872460
  • Engel, A. G., Sine, S. M. (2005). "Current understanding of congenital myasthenic syndromes." Curr Opin Pharmacol 5(3): 308-21. PubMed ID: 15907919
  • Ohno, K., et.al. (1996). "Congenital myasthenic syndrome caused by decreased agonist binding affinity due to a mutation in the acetylcholine receptor epsilon subunit." Neuron 17(1): 157-70. PubMed ID: 8755487
  • Ohno, K., et.al. (1997). "Congenital myasthenic syndromes due to heteroallelic nonsense/missense mutations in the acetylcholine receptor epsilon subunit gene: identification and functional characterization of six new mutations." Hum Mol Genet 6(5): 753-66. PubMed ID: 9158150
  • Ohno, K., et.al. (1998). "Myasthenic syndromes in Turkish kinships due to mutations in the acetylcholine receptor." Ann Neurol 44(2): 234-41. PubMed ID: 9708546
  • Ohno, K., et.al. (1999). "Congenital myasthenic syndrome caused by a mutation in the Ets-binding site of the promoter region of the acetylcholine receptor epsilon subunit gene." Neuromuscul Disord 9(3): 131-5. PubMed ID: 10382905

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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