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Primary Ciliary Dyskinesia (PCD) via the CCDC40 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11149 CCDC40 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11149CCDC4081479 81479,81479 $890 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 backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

18 days on average for standard orders or 13 days 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

  • Fang Xu, PhD, FACMG

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).

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 20 genes, including CCDC40, have been reported to cause PCD (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 & Leigh 2006). 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. Most frequently, patients with PCD have structural defects in the cilia, rendering them immotile. Bi-allelic loss-of-function mutations (nonsense, frameshift, and splicing) in CCDC40 have been shown to cause autosomal recessive PCD. CCDC40 is known to cause defects in the inner dynein arm (IDA) assembly, as well as generalized axonemal disorganization (Becker-Heck et al. 2011; Blanchon et al. 2012; Antony et al. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect at least one causative mutation in 2-5% of all patients diagnosed with PCD, or ~65% of PCD patients with IDA defects and abnormal axonemal organization (Becker-Heck et al. 2011).

Gross deletions in CCDC40 have been reported in patients with PCD (Becker-Heck et al. 2011; Blanchon et al. 2012). Clinical sensitivity cannot be estimated because only a small number of patients have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the CCDC40 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 chronic upper and lower airway infections, situs ambiguous (Ivemark Syndrome) and ultrastructural studies that point to IDA defects and axonemal disorganization (Becker-Heck et al. 2011). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CCDC40.

Gene

Official Gene Symbol OMIM ID
CCDC40 613799
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 15 613808

Citations

  • Antony D, Becker-Heck A, Zariwala MA, Schmidts M, Onoufriadis A, Forouhan M, Wilson R, Taylor-Cox T, Dewar A, Jackson C, Goggin P, Loges NT, et al. 2013. Mutations in CCDC39 and CCDC40 are the major cause of primary ciliary dyskinesia with axonemal disorganization and absent inner dynein arms. Hum. Mutat. 34: 462–472. PubMed ID: 23255504
  • Becker-Heck A, Zohn IE, Okabe N, Pollock A, Lenhart KB, Sullivan-Brown J, McSheene J, Loges NT, Olbrich H, Haeffner K, Fliegauf M, Horvath J, et al. 2011. The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nature Genetics 43: 79–84. PubMed ID: 21131974
  • Blanchon S, Legendre M, Copin B, Duquesnoy P, Montantin G, Kott E, Dastot F, Jeanson L, Cachanado M, Rousseau A, Papon JF, Beydon N, et al. 2012. Delineation of CCDC39/CCDC40 mutation spectrum and associated phenotypes in primary ciliary dyskinesia. J. Med. Genet. 49: 410–416. PubMed ID: 22693285
  • Ferkol and Leigh 2006. PubMed ID: 17142159
  • 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
  • Sutherland and Ware. 2009. PubMed ID: 19876930
  • Zariwala M.A. et al. 2013. Primary Ciliary Dyskinesia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. 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


Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

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

No Additional Test Options are available for this test.

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