Primary Ciliary Dyskinesia via the DNAAF3 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
11239 DNAAF3$890 8147981479,81479 Add to Order

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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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 and/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 and/or progressive loss of lung function.

Genetics

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 (reviewed in Ferkol & Leigh 2006). All motile cilia have inner and outer dynein arms attached at regular intervals to the nine peripheral microtubule doublets. The dynein arms consist of heavy, intermediate, and light dynein chains, and serve as molecular motors that drive microtubule sliding. Often, patients with PCD have structural defects in the inner (IDA) and/or outer dynein arms (ODA), rendering the cilia immotile and non-functional. DNAAF3 encodes a protein believed to be required for the pre-assembly of both IDA and ODA in the cytoplasm prior to their transport to the plasma membrane for incorporation into motile cilia. As a result, the motile cilia in patients with DNAAF3 mutations are missing both ODAs and IDAs (Mitchison et al. 2012). In a cohort of 112 PCD families with ODA defects, only one family (<1%) was found to have mutations in DNAAF3 (Mitchison et al. 2012). Therefore, this gene is rarely associated with PCD and should only be tested after the more commonly mutated PCD genes DNAH5 and DNAI1.

Testing Strategy

This test provides full coverage of all coding exons of the DNAAF3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Clinical Sensitivity - Sequencing with CNV

This test is predicted to detect at least one causative mutation in ~1% of all patients diagnosed with PCD (Mitchison H, et al. Nat Genet 44:381-389, 2012).

Indications for Test

This test is for patients with Primary Ciliary Dyskinesia, particularly those with both IDA and ODA structural defects (Mitchison et al. 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAAF3.

Gene

Official Gene Symbol OMIM ID
DNAAF3 614566
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 2 AR 606763

Citations

  • 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
  • Mitchison H, et al. Mutations in axonemal dynein assembly factor DNAAF3 cause primary ciliary dyskinesia. Nat Genet 44:381-389, 2012. PubMed ID: 22387996

Ordering/Specimens

Ordering Options

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.

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

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