Primary Ciliary Dyskinesia (PCD) via the DNAAF11/LRRC6 Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 11455 | DNAAF11 | 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 genetic disorder affecting the function of motile cilia (Leigh et al. 2009). The hallmark features of PCD are neonatal respiratory distress, chronic coughing, and recurrent sinus and/or ear infections; 80-100% of all PCD patients have one or more of these symptoms. In 20-50% of individuals with PCD, the major visceral organs are reversed from their normal positions (also called situs inversus) (Sutherland and Ware 2009). Kartagener’s syndrome is a condition defined by the symptomatic triad of situs inversus, sinusitis and bronchiectasis. Patients with PCD can also have abnormal orientation of some organs but not others (a condition called situs ambiguus or heterotaxy) (Kennedy et al. 2007). For more information, see GeneReviews.
Genetics
PCD is inherited most commonly in an autosomal recessive manner due to defects in motile cilia. To date, defects in at least 30 genes, including DNAAF11/LRRC6, have been reported to cause PCD (Kott et al. 2012; Horani et al. 2013; Zariwala et al. 2013). Cilia in the respiratory tract, brain and sperm flagella consist of nine peripheral microtubule doublets surrounding two central microtubules; nodal cilia in the embryo lack the central microtubules (Ferkol and Leigh 2006). All motile cilia have inner (IDA) and outer dynein arms (ODAs) attached at regular intervals to the nine peripheral microtubule doublets, which serve as molecular motors that drive microtubule sliding. Most frequently, patients with PCD have structural defects in the cilia, rendering them immotile. Loss of function variants in DNAAF11 result in absence of both the inner and outer dynein arm proteins resulting in PCD with or without situs inversus (Kott et al. 2012; Horani et al. 2013; Zariwala et al. 2013). The majority of reported pathogenic variants are chain terminating variants (nonsense, frameshift and splice-site). Missense variants in DNAAF11 have also been reported to be pathogenic (Kott et al. 2012; Horani et al. 2013; Zariwala et al. 2013).
Clinical Sensitivity - Sequencing with CNV PGxome
This test is predicted to detect two causative variants in -3-4% of all patients diagnosed with PCD, and ~11% of individuals with IDA and ODA defects (Kott et al. 2012; Zariwala et al. 2013).
Testing Strategy
This test provides full coverage of all coding exons of the DNAAF11 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 PCD, particularly those with IDA and ODA defects. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAAF11.
This test is for patients with PCD, particularly those with IDA and ODA defects. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAAF11.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| DNAAF11 | 614930 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Ciliary Dyskinesia, Primary, 19 | AR | 614935 |
Citations
- Ferkol and Leigh 2006. PubMed ID: 17142159
- Horani A, Ferkol TW, Shoseyov D, Wasserman MG, Oren YS, Kerem B, Amirav I, Cohen-Cymberknoh M, Dutcher SK, Brody SL, Elpeleg O, Kerem E. 2013. LRRC6 Mutation Causes Primary Ciliary Dyskinesia with Dynein Arm Defects. PLoS ONE 8: e59436. PubMed ID: 23527195
- Kennedy. et al. 2007. PubMed ID: 17515466
- Kott E, Duquesnoy P, Copin B, Legendre M, Dastot-Le Moal F, Montantin G, Jeanson L, Tamalet A, Papon J-F, Siffroi J-P, Rives N, Mitchell V, de Blic J, Coste A, Clement A, Escalier D, Touré A, Escudier E, Amselem S. 2012. Loss-of-Function Mutations in LRRC6, a Gene Essential for Proper Axonemal Assembly of Inner and Outer Dynein Arms, Cause Primary Ciliary Dyskinesia. The American Journal of Human Genetics 91: 958–964. PubMed ID: 23122589
- Leigh M.W. et al. 2009. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 11: 473-87. PubMed ID: 19606528
- Sutherland and Ware. 2009. PubMed ID: 19876930
- Zariwala et al. 2019. PubMed ID: 20301301
- Zariwala MA, Gee HY, Kurkowiak M, Al-Mutairi DA, Leigh MW, Hurd TW, Hjeij R, Dell SD, Chaki M, Dougherty GW, Adan M, Spear PC, Esteve-Rudd J, Loges NT, Rosenfeld M, Diaz KA, Olbrich H, Wolf WE, Sheridan E, Batten TF, Halbritter J, Porath JD, Kohl S, Lovric S, Hwang DY, Pittman JE, Burns KA, Ferkol TW, Sagel SD, Olivier KN, Morgan LC, Werner C, Raidt J, Pennekamp P, Sun Z, Zhou W, Airik R, Natarajan S, Allen SJ, Amirav I, Wieczorek D, Landwehr K, Nielsen K, Schwerk N, Sertic J, Köhler G, Washburn J, Levy S, Fan S, Koerner-Rettberg C, Amselem S, Williams DS, Mitchell BJ, Drummond IA, Otto EA, Omran H, Knowles MR, Hildebrandt F. 2013. ZMYND10 Is Mutated in Primary Ciliary Dyskinesia and Interacts with LRRC6. The American Journal of Human Genetics 93: 336–345. PubMed ID: 23891469
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
View Ordering Instructions1) Select Test Type
2) Select Additional Test Options
No Additional Test Options are available for this test.