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  • Test code: 04101
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Primary Ciliary Dyskinesia Panel

Test description

The Invitae Primary Ciliary Dyskinesia Panel analyzes up to 36 genes that are associated with primary ciliary dyskinesia (PCD), a condition characterized by chronic respiratory tract infections, infertility, and situs inversus. These genes were selected based on the available evidence to date to provide Invitae’s most comprehensive test for PCD.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (34 genes)

ARMC4 CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CFAP298 DNAAF1 DNAAF2 DNAAF3 DNAAF4 DNAAF5 DNAH1 DNAH11 DNAH5 DNAH8 DNAI1 DNAI2 DNAL1 DRC1 GAS8 LRRC6 MCIDAS NME8 OFD1 RPGR RSPH1 RSPH3 RSPH4A RSPH9 SPAG1 ZMYND10

Add-on Preliminary-evidence Gene for Primary Ciliary Dyskinesia (1 gene)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include a gene which does not currently have a definitive clinical association, but which may prove to be clinically significant in the future. This gene can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

INVS

Add-on Cystic Fibrosis Gene (1 gene)

Many of the clinical features of PCD overlap with those of cystic fibrosis, including persistent sinusitis, chronic pneumonia, and bronchiectasis. If CFTR sequencing has not previously been performed, adding the CFTR test to this analysis may be appropriate. It is recommended that patients with probable PCD should be screened for pathogenic CFTR variants to rule out the possibility of cystic fibrosis. This gene can be included at no additional charge.

CFTR

Alternative tests to consider

Nearly half of all PCD patients have some form of a congenital heart defect (CHD), (Kennedy et al. 2007) and a similarly large fraction of patients born with a CHD (30%) have some indication of PCD (Nakhleh et al. 2012). Given the significant overlap between PCD and CHD and the difficulty in differentiating between PCD and non-PCD related heart defects early in life, analyzing the genes associated with congenital heart disease may be appropriate. If clinically indicated, the Invitae Congenital Heart Disease and Heterotaxy Panel includes genes associated with congenital heart defects and ciliopathies and can be ordered instead of this panel at no additional charge.

PCD is a member of class of disorders called ciliopathies. Ciliopathies share many overlapping symptoms, often making it difficult to distinguish between them based on clinical presentation alone. Depending on the individual’s clinical and family history, the broader Invitae Ciliopathies Panel may be appropriate. It can be ordered at no additional cost.

  • primary ciliary dyskinesia (PCD)

Primary ciliary dyskinesia (PCD) is a genetic defect affecting the cilia—hair-like structures on the surface of cells. Ciliary movement in the lungs, nasal passageways, and ear canals protect the airways from infections. Ciliary movement is also important in the developing embryo as the internal organs are being positioned. Many patients with PCD are born with their internal organs reversed or mirrored from their original positions—a condition known as situs inversus totalis. Most patients present with neonatal respiratory distress during the first week of life and nearly all develop a chronic, wet-sounding cough to help compensate for the loss of ciliary movement in the lungs. Recurrent bacterial infections in the lower airways and nasal passageways often lead to chronic or recurrent pneumonia, sinusitis, and otitis media. PCD is a progressive disease that typically results in bronchiectasis, and some patients will develop severe lung disease and require a lung transplant as adults.

Approximately 50%-70% of patients with a strong clinical suspicion of PCD are expected to have a pathogenic variant in one of the genes on this panel.

The majority of PCD cases are inherited in an autosomal recessive pattern. Two genetic subtypes are inherited in an X-linked pattern:

  • RPGR is associated with a complex form of X-linked retinitis pigmentosa and PCD.
  • OFD1 is associated with a complex form of X-linked mental retardation and PCD.

Nearly all patients with a molecular diagnosis of PCD (i.e., two mutations in the same gene) have a chronic wet cough (99%), chronic nasal congestion (97%), and chronic or recurrent ear infections (92%). In most cases, these respiratory symptoms present within the first month of life, and approximately 80% of newborns with PCD require supplemental oxygen during the first 10-15 days in the hospital. About half of all individuals with PCD are found to have laterality defects, including situs inversus and heterotaxy. If left undiagnosed and untreated, most individuals will develop severe respiratory failure and will likely need a lung transplant.

The prevalence of PCD is estimated at 1 in 15,000 to 20,000 individuals.

This test may be appropriate for:

  • patients with laterality defects, such as situs inversus, situs ambiguous, or heterotaxy
  • term infants with unexplained respiratory distress
  • children with a history of a chronic, wet-sounding cough that is associated with persistent rhinosinusitus or otitis media
  • adults with bronchiectasis

  1. Lobo, J, et al. Primary ciliary dyskinesia. Semin Respir Crit Care Med. 2015; 36(2):169-79. doi: 10.1055/s-0035-1546748. PMID: 25826585
  2. Zariwala, MA, et al. Primary Ciliary Dyskinesia. 2007 Jan 24. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1122/ PMID: 20301301
  3. Leigh, MW, et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet. Med. 2009; 11(7):473-87. PMID: 19606528
  4. Davis, SD, et al. Clinical features of childhood primary ciliary dyskinesia by genotype and ultrastructural phenotype. Am. J. Respir. Crit. Care Med. 2015; 191(3):316-24. doi: 10.1164/rccm.201409-1672OC. PMID: 25493340
  5. Barbato, A, et al. Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children. Eur. Respir. J. 2009; 34(6):1264-76. doi: 10.1183/09031936.00176608. PMID: 19948909
  6. Nakhleh, N, et al. High prevalence of respiratory ciliary dysfunction in congenital heart disease patients with heterotaxy. Circulation. 2012; 125(18):2232-42. PMID: 22499950
  7. Kennedy, MP, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007; 115(22):2814-21. PMID: 17515466
  8. Moalem, S, et al. Broadening the ciliopathy spectrum: motile cilia dyskinesia, and nephronophthisis associated with a previously unreported homozygous mutation in the INVS/NPHP2 gene. Am. J. Med. Genet. A. 2013; 161A(7):1792-6. doi: 10.1002/ajmg.a.36036. PMID: 23713026

For additional information, please refer to “Treatment recommendations in Primary Ciliary Dyskinesia” (PMID: 26586601).

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ARMC4 NM_018076.2
CCDC103 NM_213607.2
CCDC114 NM_144577.3
CCDC151 NM_145045.4
CCDC39 NM_181426.1
CCDC40 NM_017950.3
CCDC65 NM_033124.4
CCNO NM_021147.4
CFAP298 NM_021254.2
CFTR* NM_000492.3
DNAAF1 NM_178452.4
DNAAF2 NM_018139.2
DNAAF3 NM_001256714.1
DNAAF4 NM_130810.3
DNAAF5 NM_017802.3
DNAH1 NM_015512.4
DNAH11 NM_001277115.1
DNAH5 NM_001369.2
DNAH8 NM_001206927.1
DNAI1 NM_012144.3
DNAI2 NM_023036.4
DNAL1 NM_031427.3
DRC1 NM_145038.3
GAS8 NM_001481.2
INVS NM_014425.3
LRRC6 NM_012472.4
MCIDAS NM_001190787.1
NME8 NM_016616.4
OFD1 NM_003611.2
RPGR* NM_000328.2
RSPH1 NM_080860.3
RSPH3 NM_031924.4
RSPH4A NM_001010892.2
RSPH9 NM_152732.4
SPAG1 NM_172218.2
ZMYND10 NM_015896.2

CFTR: Analysis includes the intronic variants: NM_000492.3:c.3718-2477C>T (also known as 3849+10kbC>T), c.1210-34TG[12]T[5] (also known as T5TG12), c.1210-34TG[11]T[5] (also known as T5TG11), and c.1679+1634A>G.
RPGR: Only the transcript associated with X-linked primary ciliary dyskinesia (XL PCD) is analyzed; therefore, this test is not appropriate for X-linked retinitis pigmentosa (XLRP) testing.