Primary Ciliary Dyskinesia (PCD) via the DNAH5 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 3073 | DNAH5 | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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
Primary Ciliary Dyskinesia is inherited most commonly in an autosomal recessive manner due to defects in motile cilia. To date, defects in at least 30 genes, including DNAH5, have been reported to cause PCD (Olbrich et al. 2002). 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 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. DNAH5 encodes a dynein heavy chain of the ODA, and biallelic pathogenic variants in DNAH5 are found in ~15-21% of individuals with PCD (Olbrich et al. 2002; Hornef et al. 2006; Failly et al. 2009). A mix of single nucleotide substitutions and small insertions/deletions have been described; most pathogenic variants result in premature protein termination (i.e. nonsense, frameshift, splicing), but missense variants located in conserved domains have also been reported to be pathogenic.
Clinical Sensitivity - Sequencing with CNV PG-Select
This test is predicted to detect two causative mutations in 15-21% of all patients diagnosed with PCD (Olbrich et al. 2002; Hornef et al. 2006; Failly et al. 2009).
Gross deletions in DNAH5 have been reported to be causative for PCD (Berg et al. 2011). Clinical sensitivity cannot be estimated precisely, but is expected to be low because only a small number of patients with these deletions have been reported.
Testing Strategy
This test provides full coverage of all coding exons of the DNAH5 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
This test is for patients with Primary Ciliary Dyskinesia, with or without situ abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAH5.
This test is for patients with Primary Ciliary Dyskinesia, with or without situ abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAH5.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| DNAH5 | 603335 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Ciliary Dyskinesia, Primary, 3 | 608644 |
Citations
- Berg JS, Evans JP, Leigh MW, Omran H, Bizon C, Mane K, Knowles MR, Weck KE, Zariwala MA. 2011. Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: Implications for application to clinical testing. Genetics in Medicine 13: 218–229. PubMed ID: 21270641
- Failly M, Bartoloni L, Letourneau A, Munoz A, Falconnet E, Rossier C, Santi MM de, Santamaria F, Sacco O, DeLozier-Blanchet CD, Lazor R, Blouin J-L. 2009. Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia. Journal of Medical Genetics 46: 281–286. PubMed ID: 19357118
- Ferkol and Leigh 2006. PubMed ID: 17142159
- Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin J-L, Bartoloni L, et al. 2006. DNAH5 Mutations Are a Common Cause of Primary Ciliary Dyskinesia with Outer Dynein Arm Defects. American Journal of Respiratory and Critical Care Medicine 174: 120–126. PubMed ID: 16627867
- Kennedy. et al. 2007. PubMed ID: 17515466
- Leigh M.W. et al. 2009. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 11: 473-87. PubMed ID: 19606528
- Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, et al. 2002. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nature Genetics 30: 143–144. PubMed ID: 11788826
- Sutherland and Ware. 2009. PubMed ID: 19876930
- Zariwala et al. 2019. PubMed ID: 20301301
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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ORDER OPTIONS
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