Primary Ciliary Dyskinesia (PCD) via the DNAI1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesPrice Test CPT CodeGene CPT Codes Copy CPT Codes STAT Prenatal
4591 DNAI1$640 8147981479,81479 Add to Order

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times 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 or ear infections or both; 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, 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 both inner and outer dynein arms attached at regular intervals to the peripheral microtubule doublets. The dynein arms consist of heavy, intermediate, and light dynein chains, which serve as molecular motors that drive microtubule sliding. Most frequently, patients with PCD have structural defects in the outer dynein arms (ODA), rendering the cilia immotile and non-functional. DNAI1 encodes a dynein intermediate chain of the ODA, and recessive variants in DNAI1 are known to cause PCD (Zariwala et al. 2001). DNAI1 consists of 20 exons (Pennarun et al. 1999) and pathogenic variants can be found throughout the gene (Zariwala et al. 2006). A mix of single nucleotide substitutions and small insertions/deletions have been described; most variants result in premature protein termination (i.e. nonsense, frameshift, splicing), but a handful of missense variants located in conserved domains also cause PCD (Human Gene Mutation Database; www.hgmd.org). To date, no gross deletions within the DNAI1 locus have been described.

Testing Strategy

This test provides full coverage of all coding exons of the DNAI1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Clinical Sensitivity - Sequencing and CNV

This test is predicted to detect at least one causative variant in ~9% of all patients diagnosed with PCD, and ~13% of PCD patients selected for ODA structural defects (Zariwala et al. 2006).

Indications for Test

This test is for patients with primary ciliary dyskinesia, with or without situs inversus. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAI1.

Gene

Official Gene Symbol OMIM ID
DNAI1 604366
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 1 AR 244400

Related Tests

Name
Heterotaxy, Situs Inversus and Kartagener's Syndrome Panel
Hydrocephalus Panel

Citations

  • Ferkol and Leigh 2006. PubMed ID: 17142159
  • Human Gene Mutation Database.
  • Leigh M.W. et al. 2009. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 11: 473-87. PubMed ID: 19606528
  • Pennarun, G., et.al. (1999). "Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia." Am J Hum Genet 65(6): 1508-19. PubMed ID: 10577904
  • Zariwala, M. A., et.al. (2006). "Mutations of DNAI1 in primary ciliary dyskinesia: evidence of founder effect in a common mutation." Am J Respir Crit Care Med 174(8): 858-66. PubMed ID: 16858015
  • Zariwala, M., et.al. (2001). "Germline mutations in an intermediate chain dynein cause primary ciliary dyskinesia." Am J Respir Cell Mol Biol 25(5): 577-83. PubMed ID: 11713099

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

loading Loading... ×

Copy Text to Clipboard
×