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Primary Ciliary Dyskinesia (PCD) via the DNAH5 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3073 DNAH5 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3073DNAH581479 81479,81479 $640 Order Options and Pricing

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.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

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). For more information, see GeneReviews.

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 30 genes, including DNAH5, have been reported to cause PCD (Olbrich et al. 2002). 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). All motile cilia have inner and outer dynein arms (ODAs) 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. DNAH5 encodes a dynein heavy chain of the ODA, and biallelic pathogenic variants in DNAH5 are found in ~15-21% of individuals with PCD (Olbrich et al. 2002; Hornef et al. 2006; Failly et al. 2009). A mix of single nucleotide substitutions and small insertions/deletions have been described; most pathogenic variants result in premature protein termination (i.e. nonsense, frameshift, splicing), but missense variants located in conserved domains have also been reported to be pathogenic.

Clinical Sensitivity - Sequencing with CNV PG-Select

This test is predicted to detect two causative mutations in 15-21% of all patients diagnosed with PCD (Olbrich et al. 2002; Hornef et al. 2006; Failly et al. 2009).

Gross deletions in DNAH5 have been reported to be causative for PCD (Berg et al. 2011). Clinical sensitivity cannot be estimated precisely, but is expected to be low because only a small number of patients with these deletions have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the DNAH5 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

This test is for patients with Primary Ciliary Dyskinesia, with or without situ abnormalities. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in DNAH5.

Gene

Official Gene Symbol OMIM ID
DNAH5 603335
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 3 608644

Citations

  • Berg JS, Evans JP, Leigh MW, Omran H, Bizon C, Mane K, Knowles MR, Weck KE, Zariwala MA. 2011. Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: Implications for application to clinical testing. Genetics in Medicine 13: 218–229. PubMed ID: 21270641
  • Failly M, Bartoloni L, Letourneau A, Munoz A, Falconnet E, Rossier C, Santi MM de, Santamaria F, Sacco O, DeLozier-Blanchet CD, Lazor R, Blouin J-L. 2009. Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia. Journal of Medical Genetics 46: 281–286. PubMed ID: 19357118
  • Ferkol and Leigh 2006. PubMed ID: 17142159
  • Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, Wildhaber J, Noone PG, Kennedy M, Antonarakis SE, Blouin J-L, Bartoloni L, et al. 2006. DNAH5 Mutations Are a Common Cause of Primary Ciliary Dyskinesia with Outer Dynein Arm Defects. American Journal of Respiratory and Critical Care Medicine 174: 120–126. PubMed ID: 16627867
  • 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
  • Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, et al. 2002. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nature Genetics 30: 143–144. PubMed ID: 11788826
  • 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

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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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