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Primary Ciliary Dyskinesia (PCD) via the CFAP300 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
15439 CFAP300 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15439CFAP30081479 81479(x2) $890 Order Options and Pricing

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).

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 with an incidence of 1 in 16,000 individuals (Leigh et al. 2009. PubMed ID: 19606528). 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 20-50% of individuals with PCD, the major visceral organs are reversed from their normal positions (also called situs inversus; Sutherland and Ware. 2009. PubMed ID: 19876930). 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 ambiguous or heterotaxy; Kennedy et al. 2007. PubMed ID: 17515466). For more information, see GeneReviews (Zariwala et al. 2019. PubMed ID: 20301301).

Individuals with biallelic CFAP300 variants displayed a consistent PCD phenotype with laterality defects and immotile respiratory cilia displaying combined loss of inner and outer dynein arms (Fassad et al. 2018. PubMed ID: 29727692; Höben et al. 2018. PubMed ID: 29727693).

The majority of PCD patients have neonatal symptoms and around half have situs inversus but, despite these signs, diagnosis is often delayed (Collins et al. 2014. PubMed ID: 26237387). This prevents early onset of regular airway clearance therapy, aggressive management of infections, monitoring and treatment of hearing impairment, and genetic counselling for the family. Genetic testing is helpful in identifying patients that need functional assessment and improving the diagnostic process.

Genetics

Primary ciliary dyskinesia is mostly inherited in an autosomal recessive manner due to defects in motile cilia. To date, defects in at least 45 genes, including CFAP300, have been reported to cause PCD (Fassad et al. 2018. PubMed ID: 29727692; Höben et al. 2018. PubMed ID: 29727693). Biallelic loss of function variants in CFAP300 are associated with autosomal recessive PCD. To our knowledge, no de novo variants have been reported in CFAP300. Variants reported to date include missense, nonsense, and small indel variants. To date, no copy number changes have been documented in the literature.

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. PubMed ID: 17142159). All motile cilia have both inner and outer dynein arms (IDAs and ODAs) attached at regular intervals to the peripheral microtubule doublets. The dynein arms (DAs) consist of heavy, intermediate, and light dynein chains and serve as molecular motors that drive microtubule sliding. Most frequently, patients with PCD have structural defects in the outer dynein arms, rendering the cilia immotile and non-functional.

CFAP300 encodes a protein essential for assembly of dynein arms. CFAP300 pathogenic variants resulted in defects of axonemal outer and inner dynein arms and ciliary immobility. Knockdown of Cfap300 in paramecium let to loss of both IDAs and ODAs and a defective swimming pattern with severely reduced velocity and significantly decreased cilia beat frequency (Fassad et al. 2018. PubMed ID: 29727692; Höben et al. 2018. PubMed ID: 29727693).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, 7 families with CFAP300 pathogenic variants have been reported. Abnormalities in CFAP300 therefore appear to be a relatively rare cause of PCD (Fassad et al. 2018. PubMed ID: 29727692; Höben et al. 2018. PubMed ID: 29727693).

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the CFAP300 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 can be considered for individuals with primary ciliary dyskinesia. Targeted testing is indicated for family members of patients who have known pathogenic variants in CFAP300. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CFAP300.

Gene

Official Gene Symbol OMIM ID
CFAP300 618058
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary dyskinesia, primary, 38 AR 618063

Citations

  • Collins et al. 2014. PubMed ID: 26237387
  • Fassad et al. 2018. PubMed ID: 29727692
  • Ferkol and Leigh. 2006. PubMed ID: 17142159
  • Höben et al. 2018. PubMed ID: 29727693
  • Kennedy et al. 2007. PubMed ID: 17515466
  • Leigh et al. 2009. PubMed ID: 19606528
  • 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


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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