Rapsyn-Related Disorders via the RAPSN Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits


Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
466 RAPSN$610.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

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

See More

See Less

Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 RAPSN$990.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

Total Price









Over 100

Call for quote

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features
Congenital myasthenic syndromes (CMS) are disorders of the neuromuscular junction resulting from defects in presynaptic, synaptic, or post synaptic 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 post synaptic 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 mutations in RAPSN (Vogt et al. Am J Hum Genet 82:222-227, 2008; Michalk et al. Am J Hum Genet 82:464-476, 2008).
Congenital myasthenic syndrome (CMS) and fetal akinesia deformation sequence due to RAPSN gene mutations are inherited as autosomal recessive disorders. One mutation, 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 mutations 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 mutation (Dunne and Maselli J Hum Genet 48:204-207, 2003). A founder mutation 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).
Testing Strategy
Rapsyn is encoded by the RAPSN gene located on chr 11p11.2. Testing is accomplished by amplifying the promoter and 8 coding exons and ~10 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard dideoxy sequencing methods and a capillary electrophoresis instrument. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.
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. Individuals with fetal akinesia sequence and autosomal recessive inheritance.


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


Genetic Counselors
  • Angela Abicht, Hanns Lochm?ller (2006). "Congenital Myasthenic Syndromes."
  • Apel, E. D., (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., (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., (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., (2006). "Impaired receptor clustering in congenital myasthenic syndrome with novel RAPSN mutations." Neurology 67(7): 1159-64. PubMed ID: 16931511
  • Ohno, K., (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., (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
Order Kits

Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

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.
  • 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.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×