• Test Code:
    1277
  • Department:
  • Test Synonyms:
    NephronophthisisOrofaciodigital syndrome type 1Senior-Loken syndromeJoubert SyndromeMeckel-Gruber syndromeBardet-Biedl syndromeHeterotaxiasPrimary Ciliary DysfunctionACVR2BAHI1AIPL1ARL13BARL6ATXN10B9D1B9D2BBS1BBS10BBS12BBS2BBS4BBS5BBS7BBS9C2orf71C5orf42 CC2D2ACCDC28BCCDC39CCDC40CDH23CEP290CEP41CFTRCITED2CLRN1CRB1CRELD1CRXDFNB31DNAAF1DNAAF2DNAAF3DNAH11DNAH5DNAI1DNAI2DNAL1DYNC2H1EVCEVC2FOXH1GATA4GDF1GLIS2GPR98GUCY2DHYLS1IFT43IFT80 IMPDH1INPP5EINVSIQCB1KCNJ13KIF7LCA5LEFTY2LRATMKKSMKS1MYO7ANEK1NEK8NKX2-5NME8NODALNPHP1NPHP3NPHP4OFD1PCDH15PKD2PKHD1RD3RDH12RPE65RPGRRPGRIP1RPGRIP1LRSPH4ARSPH9 SCNN1ASCNN1BSCNN1GSDCCAG8SHROOM3SMAD2SPATA7TCTN1TCTN2TMEM138TMEM216TMEM237TMEM67TOPORSTRIM32TSC1TSC2TTC21BTTC8TULP1UMODUSH1CUSH1GUSH2AVHLWDPCPWDR19WDR35XPNPEP3ZIC3
  • CPT Code(s):
    81408
Background:

Ciliopathies are a heterogeneous group of genetic disorders affecting multiple systems. Clinical phenotypes may include retinitis pigementosa, polydactylism, global developmental delays, cognitive impairments, brain malformations, impaired kidney function, abnormal left/right axis of the body and seizures. This class of disorders includes nephronophthisis, orofaciodigital syndrome type 1, Senior-Loken syndrome, Joubert syndrome, Meckel-Gruber syndrome, Bardet-Biedl syndrome, heterotaxias, and primary ciliary dysfunction. These conditions can be inherited in an autosomal dominant, recessive or X-linked pattern. This panel tests the coding regions for 114 genes associated with ciliopathies.

Reasons for Referral:

  • Patient display phenotypes associated with ciliopathy disorders
  • Carrier testing
  • Positive family history

Methodology:

Next generation sequencing will analyze the exons or coding regions of 114 Ciliopathies-associated genes using Illumina NextSeq 500 technology.  Samples are prepared using hybridization probes to enrich exonic regions. This assay does not assess regions of insufficient coverage, introns and promoter regions; pseudogenes; where the reference genome is inaccurate or contains gaps and insertions; and regions of high GC or polynucleotide repeats, but may contain variants that impact gene function. 

Exon-level deletion/duplication analysis is performed by running the NGS data through the Genome Analysis Toolkit (GATK) Germline Copy Number Variation best practices pipeline from GATK, version 4.1.4.1. A Bayesian model was validated clinically in our lab. The model can detect copy changes at a resolution of three (3) or more probe targets (exons) for deletions and duplications in genes that do not have pseudogenes, and is not designed to detect low-level mosaicism or balanced alterations.

The 114 Ciliopathies-associated genes are listed below:

Gene Name

Gene Coverage

ACVR2B, AHI1, AIPL1, ARL13B, ARL6, ATXN10, B9D1, B9D2, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, C2orf71, CC2D2A, CCDC28B, CCDC39, CCDC40, CDH23, CEP290, CEP41, CFTR, CLRN1, CRB1, CRELD1, CRX, DFNB31, DNAAF1, DNAAF3, DNAH11, DNAH5, DNAI1, DNAI2, DNAL1, DYNC2H1, EVC2, GLIS2, GPR98, HYLS1, IFT43, IFT80, IMPDH1, INVS, IQCB1, LCA5, LEFTY2, LRAT, MKKS, MKS1, MYO7A, NEK1, NEK8, NME8, NODAL, NPHP1, NPHP3, NPHP4, OFD1, PCDH15, PKHD1, RD3, RDH12, RPE65, RPGR, RPGRIP1, RPGRIP1L, RSPH4A, RSPH9, SCNN1A, SCNN1B, SCNN1G, SDCCAG8, SHROOM3, SMAD2, SPATA7, TCTN1, TCTN2, TMEM138, TMEM216, TMEM237, TMEM67, TOPORS, TRIM32, TSC1, TSC2, TTC21B, TTC8, TULP1, UMOD, USH1C, USH1G, USH2A, VHL, WDPCP, WDR19, WDR35, XPNPEP3, ZIC3

95%-100%

CITED2, DNAAF2, EVC, INPP5E, KCNJ13, KIF7

90%-95%

C5orf42, FOXH1, GUCY2D, NKX2-5, PKD2

75%-90%

GDF1, GATA4

50%-75%


Specimen Requirements:

Blood:  EDTA or ACD (Solution A or B):

  • Adult: 5 mL
  • Child: 5 mL
  • Infant: 2-3 mL
Saliva: 2 ORAgene™ Saliva Collection Kits (OGR-500) used according to manufacturer instructions.  Please contact KDL Client Services for a Saliva Collection Kit for patients that cannot provide a blood sample.

Assisted Saliva:
4 ORAgene™ Assisted Saliva Collection Kits (OGR-575) used according to manufacturer instructions.  Please contact KDL Client Services for an Assisted Saliva Collection Kit for patients that cannot provide a blood sample.

Skin Fibroblast: Punch Biopsy (Cell cultures will be prepared at KDL and used for testing), or 2 T-25 confluent flasks.

DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

Notice Regarding Molecular Genetic Testing on CVS or Amniotic Fluid Specimens:

  • Maternal cell rule-out testing will be performed on all prenatal specimens received. Please provide maternal blood in addition to the fetal specimen. Additional charges apply for the maternal cell rule-out test.

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Test Performed (Days):

Weekly

Turn Around Time:

8 weeks

Shipment Sensitivity Requirements:

  • Package and ship specimen to remain cold, but not frozen. 
  • Ship via overnight express, using the FedEx priority overnight label provided. 
  • Contact Client Services for shipping kits and instructions at (855) 535-1522.

References:

  1. The Ciliopathies: An Emerging Class of Human Genetic Disorders: Annu Rev Genomics Hum Genet. 2006;7:125-48.

Additional Info:

The Knight Cancer Institute at Oregon Health & Science University is a pioneer in the field of precision cancer medicine. The institute's director, Brian Druker, M.D., helped prove it was possible to shut down just the cells that enable cancer to grow. This breakthrough has made once-fatal forms of the disease manageable and transformed how cancer is treated. The OHSU Knight Cancer Institute is the only National Cancer Institute-designated Cancer Center between Sacramento and Seattle – an honor earned only by the nation's top cancer centers. It is headquarters for one of the National Cancer Institute's largest research collaboratives, SWOG, in addition to offering the latest treatments and technologies as well as hundreds of research studies and clinical trials.

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