Primary Ciliary Dyskinesia (PCD) via the RSPH4A 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
8513 RSPH4A$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 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, or progressive loss of lung function.

Genetics

Motile cilia are complex structures composed of roughly 250 proteins (reviewed in Ferkol & Leigh 2006). Planar motion cilia (i.e. from the respiratory tract, brain, and reproductive tract) consist of nine microtubule doublets that surround a central core of two microtubules (9+2 configuration). Rotary motion cilia (i.e. those in the embryonal node) lack the central core microtubules (9+0 configuration). 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. For 9+2 cilia, radial spokes form a signal-transduction scaffold between the peripheral dynein arms and the central-core microtubule pair, giving these cilia their characteristic planar (i.e. forward and backward) motion. Recessive variants in two genes encoding radial spoke proteins, RSPH4A and RSPH9, have recently been found to cause PCD (Castleman et al. 2009). The respiratory cilia in these patients either lack the central-core microtubules, having a 9+0 configuration, or have a single peripheral microtubule pair transposed into the center, resulting in an abnormal 8+1 configuration. Remarkably, the cilia in these patients have normal beat frequencies but display a rotational beat pattern, rather than the normal forward and backward planar motion. RSPH4A is comprised of 6 exons and, to date, just three nonsense variants (two in exon 1 and one in exon 3) have been described in 5 unrelated families (Castleman et al. 2009). All patients with RSPH4A variants had cilia with transposed microtubules (i.e. 8+1 configuration).

Testing Strategy

This test provides full coverage of all coding exons of the RSPH4A 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 variant in ~1-2% of all patients diagnosed with PCD and ~75% of PCD patients with central-core microtubule defects (Castleman et al. Am J Hum Genet 84:197-209, 2009).

Indications for Test

This test is for patients with primary ciliary dyskinesia, particularly those with central-core microtubule defects and normal situs laterality. For patients with situs inversus or heterotaxy, see the Kartagener's syndrome panel test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in RSPH4A.

Gene

Official Gene Symbol OMIM ID
RSPH4A 612647
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Ciliary Dyskinesia, Primary, 11 612649

Citations

  • Castleman, V. H., et.al. (2009). "Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular-pair abnormalities." Am J Hum Genet 84(2): 197-209. PubMed ID: 19200523
  • 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

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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