Primary Ciliary Dyskinesia (PCD) via the RSPH9 Gene
Summary and Pricing
Test Method
Exome Sequencing with CNV DetectionTest Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
---|---|---|---|---|---|
9037 | RSPH9 | 81479 | 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.
Clinical Features and Genetics
Clinical Features
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder affecting the function of motile cilia (reviewed by Leigh et al. 2009). Motile cilia line the upper and lower respiratory airways, the ventricular system of the brain and spinal cord, and the female fallopian tubes. They are also components of the male sperm flagellum and required for sperm motility. Ciliary movement sweeps mucus, dirt, and bacteria out of the lungs, nasal passageways, and ear canals, thus protecting them from recurrent infections. In the developing embryo, nodal cilia generate a rotational motion that determines the position of the internal organs. Without functional nodal cilia, thoracoabdominal orientation is random. The hallmark features of PCD are neonatal respiratory distress, chronic coughing, and recurrent sinus or ear infections; 80-100% of all PCD patients have one or more of these symptoms. In about 50% of individuals with PCD, the major visceral organs are reversed from their normal positions (also called situs inversus or Kartagener’s syndrome). Fetal cerebral ventriculomegaly and hydrocephalus can also occur due to impaired circulation of the cerebrospinal fluid. In adults with PCD, male infertility and female sub-fertility are also common features. Prompt diagnosis of PCD is critical for the prevention of secondary respiratory complications, such as bronchiectasis, pneumonia, or progressive loss of lung function.
Genetics
Motile cilia are complex structures composed of roughly 250 proteins (reviewed in Ferkol & Leigh 2006). Planar motion cilia (i.e. from the respiratory tract, brain, and reproductive tract) consist of nine microtubule doublets that surround a central core of two microtubules (9+2 configuration). Rotary motion cilia (i.e. those in the embryonal node) lack the central core microtubules (9+0 configuration). All motile cilia have inner and outer dynein arms attached at regular intervals to the nine peripheral microtubule doublets, which serve as molecular motors that drive microtubule sliding. For 9+2 cilia, radial spokes form a signal-transduction scaffold between the peripheral dynein arms and the central-core microtubule pair, giving these cilia their characteristic planar (i.e. forward and backward) motion. Recessive variants in two genes encoding radial spoke proteins, RSPH4A and RSPH9, have recently been found to cause PCD (Castleman et al. 2009). The respiratory cilia in these patients either lack the central-core microtubules, having a 9+0 configuration, or have a single peripheral microtubule pair transposed into the center, resulting in an abnormal 8+1 configuration. Remarkably, the cilia in these patients have normal beat frequencies but display a rotational beat pattern, rather than the normal forward and backward planar motion. RSPH9 is comprised of 5 exons, and to date, only a single homozygous nonsense variant has been described in two consanguineous Bedouin families (Castleman et al. 2009). Both of these families had respiratory cilia lacking the central core microtubules (i.e. 9+0 configuration).
Clinical Sensitivity - Sequencing with CNV PGxome
This test is predicted to detect at least one causative variant in ~1-2% of all patients diagnosed with PCD and ~25% of PCD patients with central-core microtubule defects (Castleman et al. Am J Hum Genet 84:197-209, 2009).
Testing Strategy
This test provides full coverage of all coding exons of the RSPH9 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
This test is for patients with primary ciliary dyskinesia, particularly those with central-core microtubule defects and normal situs laterality. For patients with situs inversus or heterotaxy, see the Kartagener's syndrome panel test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RSPH9.
This test is for patients with primary ciliary dyskinesia, particularly those with central-core microtubule defects and normal situs laterality. For patients with situs inversus or heterotaxy, see the Kartagener's syndrome panel test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RSPH9.
Gene
Official Gene Symbol | OMIM ID |
---|---|
RSPH9 | 612648 |
Inheritance | Abbreviation |
---|---|
Autosomal Dominant | AD |
Autosomal Recessive | AR |
X-Linked | XL |
Mitochondrial | MT |
Disease
Name | Inheritance | OMIM ID |
---|---|---|
Ciliary Dyskinesia, Primary, 12 | 612650 |
Citations
- Castleman, V. H., et.al. (2009). "Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities." Am J Hum Genet 84(2): 197-209. PubMed ID: 19200523
- Ferkol and Leigh 2006. PubMed ID: 17142159
- Leigh M.W. et al. 2009. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 11: 473-87. PubMed ID: 19606528
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
ORDER OPTIONS
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.