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Primary Ciliary Dyskinesia (PCD) via the NME8 (TXNDC3) 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
8225 NME8 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8225NME881479 81479,81479 $890 Order Options and Pricing

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.

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).

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

For Sanger Sequencing click here.

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 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; 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 subfertility 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 inner and outer dynein arms 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 outer dynein arms (ODA), rendering the cilia immotile and nonfunctional. NEM8 (TXNDC3) encodes a component of the ODA, and compound heterozygous variants in TXNDC3 have been found to cause PCD (Duriez et al. 2007). Duriez et al. recently reported that a single patient with PCD was heterozygous for a nonsense variant in exon 15 (c.1277T>A) and heterozygous for a functional polymorphism in intron 6 (c.271-27C>T). Normally, two alternative TXNDC3 mRNA isoforms are expressed: (1) a full-length isoform consisting of all 17 exons (TXNDC3fl) and (2) an isoform excluding exon 7 (TXNDC3d7). Interestingly, the c.271-27C>T variant (present in ~1% of the control subjects) was found to alter the ratio of TXNDC3fl to TXNDC3d7 isoforms. On its own, the c.271-27C>T polymorphism does not alter the TXNDC3fl/TXNDCd7 ratio enough to cause a problem. However, in combination with a clearly non-functional variant, such as the c.1277T>A nonsense variant, the c.271-27C>T variant can apparently lead to primary ciliary dyskinesia.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect at least one causative variant in ~1-2% of all patients diagnosed with PCD (Duriez et al. PNAS 104:3336-3341, 2007).

Testing Strategy

This test provides full coverage of all coding exons of the NME8 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 is for patients with primary ciliary dyskinesia. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NME8.

Gene

Official Gene Symbol OMIM ID
NME8 607421
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 6 AR 610852

Citations

  • Duriez, B., et.al. (2007). "A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia." Proc Natl Acad Sci U S A 104(9): 3336-41. PubMed ID: 17360648
  • 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

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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