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Rapsyn-Related Disorders via the RAPSN 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
7801 RAPSN 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7801RAPSN81479 81479,81479 $990 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.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

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 defects in presynaptic, synaptic, or postsynaptic proteins. Postsynaptic congenital myasthenic syndromes (OMIM 608931) can result from a deficiency or kinetic abnormality of the acetylcholine receptor. The protein rapsyn is encoded by RAPSN (OMIM 601592) and acts as a link connecting the acetylcholine receptor to the cytoskeleton-anchored dystrophin-glycoprotein complex at the neuromuscular junction, thereby stabilizing acetylcholine receptor clustering (Apel et al. Neuron 15:115-126, 1995). Clinical symptoms of postsynaptic CMS include weakness of ocular, bulbar, and limb muscles. Manifestations in the newborn period include respiratory insufficiency, poor suck and cry, feeding difficulty with choking, and facial weakness including ptosis (Abicht and Lochmüller. GeneReviews, 2006). Patients with onset in childhood show exercise-induced weakness with difficulty climbing stairs or running (Abicht and Lochmüller. GeneReviews, 2006). Fetal akinesia deformation sequence (FADS, Pena-Shokeir syndrome, type I; OMIM 208150) is characterized by prenatal-onset growth deficiency; multiple joint contractures; facial anomalies including low set and malformed ears, hypertelorism, and micrognathia; hypoplastic dermal ridges; and pulmonary hypoplasia. In some cases FADS is caused by variants in RAPSN (Vogt et al. Am J Hum Genet 82:222-227, 2008; Michalk et al. Am J Hum Genet 82:464-476, 2008).

Genetics

Congenital myasthenic syndrome (CMS) and fetal akinesia deformation sequence due to RAPSN gene variants are inherited as autosomal recessive disorders. One variant, p.Asn88Lys in exon 2, has been found repeatedly in CMS patients of European ancestry (Müller et al. J Med Genet 41:e104, 2004; Dunne and Maselli J Hum Genet 49:366-369, 2004). It should be noted that European CMS patients with RAPSN variants other than p.Asn88Lys have also been reported (Müller et al. Neurology 67: 1159-1164, 2006). A milder clinical course has been seen in patients homozygous for the common variant (Dunne and Maselli J Hum Genet 48:204-207, 2003). A founder variant of the RAPSN promoter occurs in Near-Eastern Jews and results in prognathism, malocclusion, high arched palate, and crowded teeth (Ohno et al. Hum Mol Genet 12:739-748, 2003).

Clinical Sensitivity - Sequencing with CNV PG-Select

RAPSN may account for ~20% of all CMS (Abicht and Lochmüller GeneReviews, 2006). FADS has multiple etiologies and RAPSN variants are likely a rare cause.

Testing Strategy

This test provides full coverage of all coding exons of the RAPSN 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 typical pattern of muscle weakness, decreased EMG signals with compound muscle action potential, and negative anti-acetylcholine receptor antibodies in serum and individuals with fetal akinesia sequence and autosomal recessive inheritance. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RAPSN.

Gene

Official Gene Symbol OMIM ID
RAPSN 601592
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Familial Limb Girdle Myasthenia Syndrome via the DOK7 Gene
Fetal Akinesia Deformation Sequence (FADS)/Lethal Multiple Pterygium Syndrome Panel

Citations

  • Angela Abicht, Hanns Lochm?ller (2006). "Congenital Myasthenic Syndromes."
  • Apel, E. D., et.al. (1995). "Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex." Neuron 15(1): 115-26. PubMed ID: 7619516
  • Dunne, V., Maselli, R. A. (2003). "Identification of pathogenic mutations in the human rapsyn gene." J Hum Genet 48(4): 204-7. PubMed ID: 12730725
  • Dunne, V., Maselli, R. A. (2004). "Common founder effect of rapsyn N88K studied using intragenic markers." J Hum Genet 49(7): 366-9. PubMed ID: 15252722
  • Michalk, A., et.al. (2008). "Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders." Am J Hum Genet 82(2): 464-76. PubMed ID: 18252226
  • Muller, J. S., et.al. (2004). "The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder." J Med Genet 41(8): e104. PubMed ID: 15286164
  • Muller, J. S., et.al. (2006). "Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations." Neurology 67(7): 1159-64. PubMed ID: 16931511
  • Ohno, K., et.al. (2003). "E-box mutations in the RAPSN promoter region in eight cases with congenital myasthenic syndrome." Hum Mol Genet 12(7): 739-48. PubMed ID: 12651869
  • Vogt, J., et.al. (2008). "Mutation analysis of CHRNA1, CHRNB1, CHRND, and RAPSN genes in multiple pterygium syndrome/fetal akinesia patients." Am J Hum Genet 82(1): 222-7. PubMed ID: 18179903

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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STAT and Prenatal Test Options are not available with Patient Plus.

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