Test code: KI0701
The Blueprint Genetics Ciliopathy Panel is an 83 gene test for genetic diagnostics of patients with clinical suspicion of Bardet-Biedl syndrome, cystic kidneys, Joubert syndrome, Meckel syndrome, nephronophthisis with retinal dystrophy, primary ciliary dyskinesia or situs inversus.
The panel covers genes associated with autosomal recessive, autosomal dominant and X-linked forms of ciliopathies. This comprehensive Panel includes Primary Ciliary Dyskinesia, Nephronophtisis, Senior-Loken Syndrome, Bardet-Biedl Syndrome, Joubert Syndrome and Meckel Syndrome Panels.
Ciliopathies comprise a group of disorders associated with genetic mutations encoding defective proteins, which result in either abnormal formation or function of cilia. Ciliary gene mutations are now known to cause single organ disease, as well as complex syndromes. Ciliopathies have a broad range of phenotypes encompassing a number of different autosomal recessive, dominant and X-linked syndromes. As cilia are a component of almost all cells, ciliary dysfunction can manifest as a collection of features that include primarily retinal degeneration, renal disease and cerebral anomalies. Additional manifestations include congenital fibrocystic diseases of the liver and pancreas, diabetes, obesity and skeletal dysplasias. Phenotypically heterogeneous, ciliopathic features can manifest from variation at a single locus while mutations affecting a number of different loci can, at the same time, result in similar phenotypes. Ciliopathies can be classified according to whether there is aberrant function in an intact cilium or complete absence/loss of the mature cilium. The latter is the case with severe multi-organ phenotypes. Classical ciliopathies include polycystic kidney disease (PKD), retinal degeneration, laterality defects, chronic respiratory problems, situs inversus, hydrocephalus and infertility.
Results in 3-4 weeks.
|ARL6||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||9||21|
|BBS2||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||30||84|
|C5ORF42||Orofaciodigital syndrome, Joubert syndrome||AR||63|
|CC2D2A||COACH syndrome, Joubert syndrome, Meckel syndrome||AR||64||80|
|CEP290*||Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome||AR||79||252|
|CSPP1||Jeune Asphyxiating Thoracic Dystrophy, Joubert syndrome||AR||22||23|
|DNAAF3||Primary ciliary dyskinesia||AD/AR||3||3|
|DRC1||Primary ciliary dyskinesia||AD/AR||3||2|
|HYDIN*||Primary ciliary dyskinesia||AD/AR||3||13|
|IFT172||Retinitis pigmentosa, Short -rib thoracic dysplasia with or without polydactyly||AR||18||21|
|INPP5E||Joubert syndrome, Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome)||AR||19||41|
|KIAA0586||Short rib thoracic dysplasia with polydactyly, Joubert syndrome||AR||14||26|
|KIF7||Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome||AR/Digenic||13||39|
|MKKS||Bardet-Biedl syndrome, McKusick-Kaufman syndrome||AR||13||57|
|MKS1||Bardet-Biedl syndrome, Meckel syndrome||AR||39||47|
|NPHP1||Nephronophthisis, Joubert syndrome, Senior-Loken syndrome||AR||12||64|
|NPHP3||Nephronophthisis, Renal-hepatic-pancreatic dysplasia, Meckel syndrome||AR||20||71|
|NPHP4||Nephronophthisis, Senior-Loken syndrome||AR||10||104|
|OFD1||Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome||XL||129||148|
|RPGRIP1L||COACH syndrome, Joubert syndrome, Meckel syndrome, Retinal degeneration in ciliopathy, modifier||AD/AR||28||41|
|SDCCAG8||Bardet-Biedl syndrome, Senior-Loken syndrome||AR||12||18|
|SPAG1||Primary ciliary dyskinesia||AD/AR||7||10|
|TCTN2||Joubert syndrome, Meckel syndrome||AR||15||13|
|TCTN3||Orofaciodigital syndrome (Mohr-Majewski syndrome), Joubert syndrome||AR||8||10|
|TMEM67||Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndrome||AR||78||138|
|TMEM216||Joubert syndrome, Meckel syndrome||AR||8||8|
|TMEM231||Joubert syndrome, Meckel syndrome||AR||7||16|
|TRIM32||Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle||AR||7||15|
|TTC8||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||5||16|
|TTC21B||Short-rib thoracic dysplasia, Nephronophthisis||AR||6||47|
|WDR19||Retinitis pigmentosa, Nephronophthisis, Short -rib thoracic dysplasia with or without polydactyly, Senior-Loken syndrome||AD/AR||16||25|
|ZNF423||Nephronophthisis, Joubert syndrome||AD/AR||7||6|
- * Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.
Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.
Blueprint Genetics offers a comprehensive ciliopathy panel that covers classical genes associated with Bardet-Biedl syndrome, cystic kidneys, Joubert syndrome, Meckel syndrome, nephronophthisis with retinal dystrophy, primary ciliary dyskinesia and situs inversus. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.
Please see our latest validation report showing sensitivity and specificity for SNPs and indels, sequencing depth, % of the nucleotides reached at least 15x coverage etc. If the Panel is not present in the report, data will be published when the Panel becomes available for ordering. Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. All the Panels available for ordering have sensitivity and specificity higher than > 0.99 to detect single nucleotide polymorphisms and a high sensitivity for indels ranging 1-19 bp. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile. Detection limit for Del/Dup analysis varies through the genome from one to six exon Del/Dups depending on exon size, sequencing coverage and sequence content.
The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).
Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.
In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.
Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.
A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.
We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.
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ICD & CPT codes
Commonly used ICD-10 codes when ordering the Ciliopathy Panel
|Q34.8||Primary ciliary dyskinesia|
|Q61.5||Nephronophthisis with retinal dystrophy|
Accepted sample types
- EDTA blood, min. 1 ml
- Purified DNA, min. 5μg
- Saliva (Oragene DNA OG-500 kit)
Label the sample tube with your patient’s name, date of birth and the date of sample collection.
Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.