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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 6995 | CHRNE | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks 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.
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.
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 |
Diseases
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
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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