Primary Ciliary Dyskinesia (PCD) via the RPGR 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
11015 RPGR$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

PCD is most often inherited in an autosomal recessive pattern. Occasionally, however, symptoms of PCD and retinitis pigmentosa (RP; OMIM 268000) co-segregate in an X-linked pattern (Zito et al. 2003; Moore et al. 2006). RPGR, located on the X chromosome, encodes the retinitis pigmentosa GTPase regulator (Meindl et al. 1996). Loss-of-function variants in RPGR can disrupt the structure of both photoreceptor-connecting clia and motile cilia (Hong et al. 2003), thus leading to a combined RP and PCD condition (Moore et al. 2006). Males hemizygous for RPGR variants often display early onset retinal degeneration, hearing loss, recurrent sinusitis, and chronic chest infections. Female carriers of heterozygous RPGR variants may also suffer from mild symptoms of PCD or RP, including late-onset retinal degeneration, recurrent sinusitis minus chest infections, and progressive hearing loss. The RPGR gene encodes several alternatively spliced isoforms. These include isoform A (CCDS14246.1), consisting of 19 exons, and isoform C (CCDS35229.1), consisting of 15 exons. Exons 1-14 are the same for both isoforms. However, isoform A uses a cryptic donor splice site in exon 15, resulting in a short (152 nucleotides) exon 15 and inclusion of exons 16-19. By contrast, isoform C does not use the cryptic donor splice site, resulting in an extended exon 15 (also called ORF15 in the literature) with 1706 nucleotides of coding sequence (see Bader et al. 2003 for a detailed description of the ORF15 exon). Importantly, because isoform C (with ORF15) is preferentially expressed in retina and isoform A (without ORF15) is expressed throughout the respiratory tract, variants in ORF15 lead to X-linked RP without symptoms of PCD while variants in exons 1-14 lead to XLRP with additional PCD symptoms.

Testing Strategy

This test provides full coverage of all coding exons of the RPGR 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 a causative variant in about 10% of patients with apparently X-linked PCD (Moore et al. J Med Genet 43:326-333, 2006), or ~50-60% of all patients diagnosed with X-linked RP (Bader et al. Invest Ophthalmol Vis Sci 44:1458-1463, 2003).

Indications for Test

This test is for patients displaying X-linked inheritance of retinitis pigmentosa and symptoms of primary ciliary dyskenesia (Rozet et al. 2002; Moore et al. 2006).

Gene

Official Gene Symbol OMIM ID
RPGR 312610
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
Retinitis Pigmentosa (includes RPGR ORF15) Panel
Specialized Sequencing of the Mutational Hotspot RPGR (isoform C) ORF15 Region
X-linked Retinitis Pigmentosa (XLRP) via the RP2 Gene
X-linked Retinitis Pigmentosa (XLRP) via the RPGR (includes ORF15) Gene

Citations

  • Bader I. 2003. X-linked Retinitis Pigmentosa: RPGR Mutations in Most Families with Definite X Linkage and Clustering of Mutations in a Short Sequence Stretch of Exon ORF15. Investigative Ophthalmology & Visual Science 44: 1458–1463. PubMed ID: 12657579
  • Hong, D. H., et.al. (2003). "RPGR isoforms in photoreceptor connecting cilia and the transitional zone of motile cilia." Invest Ophthalmol Vis Sci 44(6): 2413-21. PubMed ID: 12766038
  • Leigh M.W. et al. 2009. Genetics in Medicine : Official Journal of the American College of Medical Genetics. 11: 473-87. PubMed ID: 19606528
  • Meindl A, Dry K, Herrmann K, Manson F, Ciccodicola A, Edgar A, Carvalho MR, Achatz H, Hellebrand H, Lennon A, Migliaccio C, Porter K, et al. 1996. A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nat. Genet. 13: 35–42. PubMed ID: 8673101
  • Moore A. 2006. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. Journal of Medical Genetics 43: 326-333. PubMed ID: 16055928
  • Rozet, J. M., et.al. (2002). "Dominant X linked retinitis pigmentosa is frequently accounted for by truncating mutations in exon ORF15 of the RPGR gene." J Med Genet 39(4): 284-5. PubMed ID: 11950860
  • Zito, I., et.al. (2003). "RPGR mutation associated with retinitis pigmentosa, impaired hearing, and sinorespiratory infections." J Med Genet 40(8): 609-15. PubMed ID: 12920075

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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