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Primary Ciliary Dyskinesia (PCD) via the GAS8 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
13059 GAS8 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
13059GAS881479 81479,81479 $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 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. PubMed ID: 19876930). The similar 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).

The majority of PCD patients have neonatal symptoms and around half have situs inversus (Collins et al. 2014. PubMed ID: 26237387). Despite these signs, diagnosis is often delayed. 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.

Genetics

Primary Ciliary Dyskinesia is mostly inherited in an autosomal recessive manner due to defects in motile cilia. To date, defects in at least 40 genes, including GAS8, have been reported to cause PCD (Olbrich et al. 2015. PubMed ID: 26387594; Jeanson et al. 2016. PubMed ID: 27120127; Lewis et al. 2016. PubMed ID: 27472056). Pathogenic variants reported in GAS8 include loss of function variants consisting of nonsense, frameshift, and missense pathogenic variants. No copy number or de novo variants have been reported.

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 attached at regular intervals to the peripheral microtubule doublets. The dynein arms 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.

GAS8 encodes a subunit of the nexin-dynein regulatory complex (N-DRC) that plays an important structural and functional role in ciliary movement. Pathogenic variants in GAS8 disrupt the N-DRC and cause axonemal disorganization (Olbrich et al. 2015. PubMed ID: 26387594; Jeanson et al. 2016. PubMed ID: 27120127). Individuals with biallelic loss-of-function variants in GAS8 have been reported to have primary ciliary dyskinesia without situ abnormalities. Affected individuals do not have a clear ultrastructural defect on electron microscopy, but are reported to have subtle abnormalities of ciliary beating and ultrastructure (Olbrich et al. 2015. PubMed ID: 26387594; Jeanson et al. 2016. PubMed ID: 27120127; Lewis et al. 2016. PubMed ID: 27472056). GAS8 has been cited as a conditional gene for growth of human tissue culture cells (Online Gene Essentiality).

gas8-null zebrafish embryos showed hydrocephalus, left-right axis defects, and abnormal otolith composition of the inner ear, consistent with ciliary beating defects (Colantonio et al. 2009. PubMed ID: 19043402). Mice with Gas8 pathogenic variants presented with severe motility defects and PCD like symptoms including situs inversus and hydrocephalus (Lewis et al. 2016. PubMed ID: 27472056).

Clinical Sensitivity - Sequencing with CNV PGxome

To date, pathogenic variants in GAS8 have been reported in only a few patients with PCD (Olbrich et al. 2015. PubMed ID: 26387594; Jeanson et al. 2016. PubMed ID: 27120127; Lewis et al. 2016. PubMed ID: 27472056). Abnormalities in GAS8 therefore appear to be a relatively rare cause of PCD.

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 GAS8 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 GAS8. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in GAS8.

Gene

Official Gene Symbol OMIM ID
GAS8 605178
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 33 AR 616726

Citations

  • Colantonio et al. 2009. PubMed ID: 19043402
  • Collins et al. 2014. PubMed ID: 26237387
  • Ferkol and Leigh. 2006. PubMed ID: 17142159
  • Jeanson et al. 2016. PubMed ID: 27120127
  • Kennedy et al. 2007. PubMed ID: 17515466
  • Leigh et al. 2009. PubMed ID: 19606528
  • Lewis et al. 2016. PubMed ID: 27472056
  • Lewis et al. 2016. PubMed ID: 27472056
  • Olbrich et al. 2015. PubMed ID: 26387594
  • Online Gene Essentiality.
  • 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.
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