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Congenital Myasthenic Syndromes via the CHRNB1 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
CHRNB1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11173CHRNB181479 81479,81479 $990 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 platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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.

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 at onset and by negative serology tests for anti-acetylcholine receptor (AchR) and anti-Musk antibodies.

Genetics

Abnormalities of proteins involved with neuromuscular transmission underlie 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. CHRNB1 gene variants have been found in patients with slow channel CMS (Engel and Sine Curr Opinion in Pharmacol 5:308-321, 2005). CHRNB1-associated slow channel CMS (OMIM 601462) has been shown to be inherited as a recessive disorder secondary to loss-of-function variants (Quiram et al. J Clin Invest 104:1403-1410, 1999), or as a dominant disorder secondary to gain-of-function variants (Gomez et al. Ann Neurol 39:712-723, 1996; Engel et al. Hum Molec Genet 5:1217-1227, 1996). Null and low expressor CHRNB1 variants in the homozygous or compound heterozygous state lead to CMS with end-plate AChR deficiency (Quiram et al. 1999).

The beta subunit of the acetylcholine receptor is encoded by exons 1 – 11 of the CHRNB1 gene (OMIM 100710) located on chr 17p12.

Clinical Sensitivity - Sequencing with CNV PGxome

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). CHRNB1 is a rare cause of CMS.

Testing Strategy

This test provides full coverage of all coding exons of the CHRNB1 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

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 CHRNB1.

Gene

Official Gene Symbol OMIM ID
CHRNB1 100710
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • 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). "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
  • Gomez-Abad C, Gomez-Garre P, Gutierrez-Delicado E, Saygi S, Michelucci R, Tassinari CA, Rodriguez de Cordoba S, Serratosa JM. 2005. Lafora disease due to EPM2B mutations: A clinical and genetic study. Neurology 64: 982986. PubMed ID: 8651643
  • Quiram, P. A., et.al. (1999). "Mutation causing congenital myasthenia reveals acetylcholine receptor beta/delta subunit interaction essential for assembly." J Clin Invest 104(10): 1403-10. PubMed ID: 10562302

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

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2) Select Additional Test Options

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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