Invitae Ciliopathies Panel

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  • Test code: 04102
  • 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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Test description

The Invitae Ciliopathies Panel analyzes 102 genes that are important for the development and maintenance of the primary cilium. These genes are associated with a group of disorders known as ciliopathies, and were selected, based on the available evidence to date, to provide a comprehensive test for the diagnosis of these disorders.

Ciliopathies share many overlapping symptoms, which makes clinical distinction between them difficult to determine. The Invitae Ciliopathies panel test may be indicated for patients whose clinical features can be associated with one of several ciliopathies, including primary ciliary dyskinesia (PCD), Joubert syndrome and related disorders (JSRD), Bardet-Biedl syndrome (BBS), nephronophthisis (NPHP), Meckel syndrome (MKS), and skeletal ciliopathies such as asphyxiating (ATD) or short-rib thoracic dystrophy (SRTD), cranioectodermal dysplasia (CED), or Ellis-van Creveld syndrome (EVC).

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 (102 genes)

AHI1 ANKS6 ARL13B ARL6 ARMC4 B9D1 B9D2 BBS1 BBS10 BBS12 BBS2 BBS4 BBS5 BBS7 BBS9 C21orf59 C5orf42 CC2D2A CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CEP104 CEP120 CEP164 CEP290 CEP41 CEP83 CSPP1 DCDC2 DNAAF1 DNAAF2 DNAAF3 DNAAF5 DNAH1 DNAH11 DNAH5 DNAH8 DNAI1 DNAI2 DNAL1 DRC1 DYNC2H1 DYX1C1 EVC EVC2 GAS8 GLIS2 IFT122 IFT140 IFT172 IFT80 INPP5E INVS IQCB1 KIAA0586 KIF7 LRRC6 MCIDAS MKKS MKS1 MRE11 NEK1 NEK8 NME8 NPHP1 NPHP3 NPHP4 OFD1 PDE6D PKD2 PKHD1 RPGR RPGRIP1L RSPH1 RSPH3 RSPH4A RSPH9 SDCCAG8 SPAG1 TCTN1 TCTN2 TCTN3 TMEM138 TMEM216 TMEM231 TMEM237 TMEM67 TRIM32 TTC21B TTC8 WDPCP WDR19 WDR34 WDR35 WDR60 XPNPEP3 ZMYND10 ZNF423

BBS9: Deletion/duplication analysis is not offered for exon 4
CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.
MKS1: Analysis includes the intronic variant NM_017777.3: c.1408-35_1408-7del.
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.

  • asphyxiating thoracic dystrophy (ATD)
  • Bardet-Biedl syndrome (BBS)
  • cranioectodermal dysplasia (CED)
  • Ellis-van Creveld syndrome (EVC)
  • Joubert syndrome and related disorders (JSRD) and Meckel-Gruber syndrome (MKS)
  • Mainzer-Saldino syndrome (MZSDS)
  • nephronophthisis (NPHP)
  • oral-facial-digital disorder (OFD)
  • oral-facial digital syndrome type IV (OFD IV)
  • polycystic kidney disease (PKD)
  • primary ciliary dyskinesia (PCD)
  • Senior-Loken syndrome (SLSN)
  • short rib thoracic dystrophy (SRTD)
  • Weyers acrofacial dysostosis (WAD)

Ciliopathies are a class of pediatric developmental disorders that are caused by impaired function or structure of cilia. Cilia are hair-like structures on the surface of cells. Because cilia are a component of nearly all cells, abnormal formation or function of cilia can cause disease in any organ, though the organs most often affected are the eyes, ears, liver, kidney, lungs and brain. Additional symptoms may include intellectual disability, diabetes, obesity, situs inversus, polydactyly, and skeletal dysplasias.

The clinical sensitivity of this panel depends in part on the clinical diagnosis of the patient. Specific information about the diagnostic yield for each clinical phenotype is summarized in the table below.

DisorderDiagnostic yield in associated genes
Bardet-Biedl syndrome (BBS) ~80%
Cranioectodermal dysplasia (CED) ~40%
Ellis–van Creveld syndrome (EVC); ~85%
Weyers acrofacial dysostosis (WAD)
Joubert syndrome and related disorders (JSRD) including Meckel-Gruber syndrome (MKS) ~60-70%
Mainzer–Saldino syndrome (MZSDS) ~50%
Nephronophthisis (NPHP) ~30%
Oral-facial-digital disorder (OFD) ~85%
Oral-facial digital syndrome type IV (OFD IV) ~50%
Polycystic kidney disease, type 2 (ADPKD) 15% (PKD2)
Primary ciliary dyskinesia (PCD) ~50%-70%
Senior-Loken syndrome (SLSN) ~30%
Short rib thoracic dystrophy (SRTD) and asphyxiating thoracic dystrophy (ATD) ~50%

The majority of ciliopathies are inherited in an autosomal recessive manner. OFD1-related Joubert syndrome and RPGR-related ciliopathy are inherited in an X-linked manner. PKD1- and PKD2-related polycystic kidney disease are inherited in an autosomal dominant manner.

Ciliopathy disorders are typically highly penetrant conditions with variable clinical expressivity, even among members of the same family. Some clinical features may be present at birth while others manifest later in life.

The overall proportion of the population with a cilia-related disorder is currently unknown.

  • The prevalence of PCD is estimated at 1 in 15,000 to 20,000 individuals.
  • The prevalence of a cilia-related kidney disease ranges from 1:1000 for autosomal dominant polycystic kidney disease to 1:50,000 for nephronophthisis.
  • The prevalence of syndromic ciliopathies, such as BBS, JSRD and MKS is significantly lower—in the 1:80,000 to 1:100,000 range.
  • The skeletal ciliopathies are rare disorders with a collective prevalence estimated between 1:200,000 to 1:1,000,000. The prevalence is higher in populations that are isolated or have high rates of consanguinity.

  1. Arts, H, Knoers, N. Cranioectodermal Dysplasia. 2013 Sep 12. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK154653/ PMID: 24027799
  2. 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
  3. D'Asdia, MC, et al. Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis. Eur J Med Genet. 2013; 56(2):80-7. PMID: 23220543
  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. Forsythe, E, Beales, PL. Bardet-Biedl Syndrome. 2003 Jul 14. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1363/ PMID: 20301537
  6. Harris, PC, Torres, VE. Polycystic Kidney Disease, Autosomal Dominant. 2002 Jan 10. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1246/ PMID: 20301424
  7. Hildebrandt, F, et al. Ciliopathies. N. Engl. J. Med. 2011; 364(16):1533-43. doi: 10.1056/NEJMra1010172. PMID: 21506742
  8. Huber, C, Cormier-Daire, V. Ciliary disorder of the skeleton. Am J Med Genet C Semin Med Genet. 2012; 160C(3):165-74. PMID: 22791528
  9. Huber, C, et al. WDR34 mutations that cause short-rib polydactyly syndrome type III/severe asphyxiating thoracic dysplasia reveal a role for the NF-κB pathway in cilia. Am. J. Hum. Genet. 2013; 93(5):926-31. PMID: 24183449
  10. 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
  11. Leigh, MW, et al. Clinical and genetic aspects of primary ciliary dyskinesia/Kartagener syndrome. Genet. Med. 2009; 11(7):473-87. PMID: 19606528
  12. Lin, AE, et al. Sensenbrenner syndrome (Cranioectodermal dysplasia): clinical and molecular analyses of 39 patients including two new patients. Am. J. Med. Genet. A. 2013; 161A(11):2762-76. PMID: 24123776
  13. 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
  14. Logan, CV, et al. Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Mol. Neurobiol. 2011; 43(1):12-26. doi: 10.1007/s12035-010-8154-0. PMID: 21110233
  15. McInerney-Leo, AM, et al. Short-rib polydactyly and Jeune syndromes are caused by mutations in WDR60. Am. J. Hum. Genet. 2013; 93(3):515-23. PMID: 23910462
  16. 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
  17. 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
  18. Oberklaid, F, et al. Asphyxiating thoracic dysplasia. Clinical, radiological, and pathological information on 10 patients. Arch. Dis. Child. 1977; 52(10):758-65. PMID: 931421
  19. Parisi, M, Glass, I. Joubert Syndrome and Related Disorders. 2003 Jul 09. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1325/ PMID: 20301500
  20. Perrault, I, et al. Mainzer-Saldino syndrome is a ciliopathy caused by IFT140 mutations. Am. J. Hum. Genet. 2012; 90(5):864-70. PMID: 22503633
  21. Thomas, S, et al. TCTN3 mutations cause Mohr-Majewski syndrome. Am. J. Hum. Genet. 2012; 91(2):372-8. PMID: 22883145
  22. Tompson, SW, et al. Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. Hum. Genet. 2007; 120(5):663-70. PMID: 17024374
  23. Toriello, HV, Franco, B. Oral-Facial-Digital Syndrome Type I. 2002 Jul 24. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1188/ PMID: 20301367
  24. Valencia, M, et al. Widening the mutation spectrum of EVC and EVC2: ectopic expression of Weyer variants in NIH 3T3 fibroblasts disrupts Hedgehog signaling. Hum. Mutat. 2009; 30(12):1667-75. PMID: 19810119
  25. Valente, EM, et al. Primary cilia in neurodevelopmental disorders. Nat Rev Neurol. 2014; 10(1):27-36. doi: 10.1038/nrneurol.2013.247. PMID: 24296655
  26. 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

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, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AHI1 NM_017651.4
ANKS6 NM_173551.4
ARL13B NM_182896.2
ARL6 NM_177976.2
ARMC4 NM_018076.2
B9D1 NM_015681.3; NM_001243473.1
B9D2 NM_030578.3
BBS1 NM_024649.4
BBS10 NM_024685.3
BBS12 NM_152618.2
BBS2 NM_031885.3
BBS4 NM_033028.4
BBS5 NM_152384.2
BBS7 NM_176824.2
BBS9* NM_198428.2
C21orf59 NM_021254.2
C5orf42 NM_023073.3
CC2D2A NM_001080522.2
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
CEP104 NM_014704.3
CEP120 NM_153223.3
CEP164 NM_014956.4
CEP290* NM_025114.3
CEP41 NM_018718.2
CEP83 NM_016122.2
CSPP1 NM_024790.6
DCDC2 NM_016356.4
DNAAF1 NM_178452.4
DNAAF2 NM_018139.2
DNAAF3 NM_001256714.1
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
DYNC2H1 NM_001080463.1
DYX1C1 NM_130810.3
EVC NM_153717.2
EVC2 NM_147127.4
GAS8 NM_001481.2
GLIS2 NM_032575.2
IFT122 NM_052985.3
IFT140 NM_014714.3
IFT172 NM_015662.2
IFT80 NM_020800.2
INPP5E NM_019892.4
INVS NM_014425.3
IQCB1 NM_001023570.2
KIAA0586 NM_001244189.1
KIF7 NM_198525.2
LRRC6 NM_012472.4
MCIDAS NM_001190787.1
MKKS NM_018848.3
MKS1* NM_017777.3
MRE11 NM_005591.3
NEK1 NM_012224.2; NM_001199397.1
NEK8 NM_178170.2
NME8 NM_016616.4
NPHP1 NM_000272.3
NPHP3 NM_153240.4
NPHP4 NM_015102.4
OFD1 NM_003611.2
PDE6D NM_002601.3
PKD2 NM_000297.3
PKHD1 NM_138694.3
RPGR* NM_000328.2
RPGRIP1L NM_015272.2
RSPH1 NM_080860.3
RSPH3 NM_031924.4
RSPH4A NM_001010892.2
RSPH9 NM_152732.4
SDCCAG8 NM_006642.3
SPAG1 NM_172218.2
TCTN1 NM_001082538.2
TCTN2 NM_024809.4
TCTN3 NM_015631.5
TMEM138 NM_016464.4
TMEM216 NM_001173990.2
TMEM231 NM_001077416.2
TMEM237 NM_001044385.2
TMEM67 NM_153704.5
TRIM32 NM_012210.3
TTC21B NM_024753.4
TTC8 NM_198309.3
WDPCP NM_015910.5
WDR19 NM_025132.3
WDR34 NM_052844.3
WDR35 NM_001006657.1
WDR60 NM_018051.4
XPNPEP3 NM_022098.3
ZMYND10 NM_015896.2
ZNF423 NM_015069.3

BBS9: Deletion/duplication analysis is not offered for exon 4
CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.
MKS1: Analysis includes the intronic variant NM_017777.3: c.1408-35_1408-7del.
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.