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.
AHI1 ANKS6 ARL13B ARL6 ARMC4 B9D1 B9D2 BBS1 BBS10 BBS12 BBS2 BBS4 BBS5 BBS7 BBS9 CC2D2A CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CEP104 CEP120 CEP164 CEP290 CEP41 CEP83 CFAP298 CPLANE1 CSPP1 DCDC2 DNAAF1 DNAAF2 DNAAF3 DNAAF4 DNAAF5 DNAH1 DNAH11 DNAH5 DNAH8 DNAI1 DNAI2 DNAL1 DRC1 DYNC2H1 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
AHI1 ANKS6 ARL13B ARL6 ARMC4 B9D1 B9D2 BBS1 BBS10 BBS12 BBS2 BBS4 BBS5 BBS7 BBS9 CC2D2A CCDC103 CCDC114 CCDC151 CCDC39 CCDC40 CCDC65 CCNO CEP104 CEP120 CEP164 CEP290 CEP41 CEP83 CFAP298 CPLANE1 CSPP1 DCDC2 DNAAF1 DNAAF2 DNAAF3 DNAAF4 DNAAF5 DNAH1 DNAH11 DNAH5 DNAH8 DNAI1 DNAI2 DNAL1 DRC1 DYNC2H1 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
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.
Disorder | Diagnostic 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.
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 |
---|---|---|---|
AHI1 | NM_017651.4 | ||
ANKS6 | NM_173551.4 | ||
ARL13B | NM_182896.2 | ||
ARL6 | NM_177976.2 | ||
ARMC4 | NM_018076.2 | ||
B9D1 | NM_015681.3 | ||
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 | ||
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 | ||
CFAP298 | NM_021254.2 | ||
CPLANE1 | NM_023073.3 | ||
CSPP1 | NM_024790.6 | ||
DCDC2 | NM_016356.4 | ||
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 | ||
DYNC2H1 | NM_001080463.1 | ||
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 | ||
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.