Cone Rod Dystrophy Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: OP0401

The Blueprint Genetics Cone Rod Dystrophy Panel is a 32 gene test for genetic diagnostics of patients with clinical suspicion of cone rod dystrophy.

The panel covers genes associated with autosomal recessive, autosomal dominant and X-linked forms of cone rod dystrophy. This panel is included in the Retinal Dystrophy Panel.

About Cone Rod Dystrophy

Cone rod dystrophies (CRD) are inherited retinal dystrophies characterized by cone dysfunction followed by rod photoreceptor degeneration. Fundus examination shows pigment deposits and retinal atrophy in the macular region of the retina. In contrast to typical retinitis pigmentosa (RP, rod cone dystrophy) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. Predominant symptoms of CRDs are decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RP, leading to earlier legal blindness and disability. CRDs are most frequently nonsyndromic, but they may also be part of several syndromes, such as Bardet-Biedl syndrome. Nonsyndromic CRDs can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. The two major causative genes involved in the pathogenesis of CRDs are ABCA4 (autosomal recessive CRD, also implicated in Stargardt disease) and GUCY2D (autosomal dominant CRD). The prevalence of CRDs is estimated at 1:40,000.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Cone Rod Dystrophy Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
ABCA4 Stargardt disease, Retinitis pigmentosa, Cone rod dystrophy, Retinal dystrophy, early-onset severe, Fundus flavimaculatus AR 203 1012
ADAM9 Cone rod dystrophy AR 5 9
AIPL1 Retinitis pigmentosa, Cone rod dystrophy, Leber congenital amaurosis AD/AR 8 73
BEST1 Vitreoretinochoroidopathy, Microcornea, Rod-cone dystrophy, Posterior staphyloma, Bestrophinopathy, Vitelliform macular dystrophy, Cataract, Retinitis pigmentosa AD/AR 31 269
C8ORF37 Retinitis pigmentosa, Cone rod dystrophy AR 4
CABP4 Night blindness, congenital stationary AR 4 10
CACNA1F Aland Island eye disease, Cone rod dystrophy, Night blindness, congenital stationary XL 18 142
CACNA2D4 Retinal cone dystrophy AR 1 9
CDHR1 Retinitis pigmentosa, Cone rod dystrophy AR 9 33
CERKL Retinitis pigmentosa AR 10 26
CLN3 Ceroid lipofuscinosis, neuronal AR 69 64
CNGA3 Leber congenital amaurosis, Achromatopsia AR 16 141
CNGB3 Macular degeneration, juvenile, Achromatopsia AR 14 63
CNNM4 Jalili syndrome AR 9 18
CRB1 Retinitis pigmentosa, Pigmented paravenous chorioretinal atrophy, Leber congenital amaurosis AD/AR 31 291
CRX Cone rod dystrophy, Leber congenital amaurosis AD/AR 22 87
CYP4V2 Retinitis pigmentosa, Bietti crystalline corneoretinal dystrophy AR 30 75
FBLN5 Cutis laxa, Macular degeneration, age-related AD/AR 13 21
GNAT2 Achromatopsia AR 4 11
GUCA1A Cone dystrophy 3/Cone rod dystrophy AD 5 16
GUCY2D Cone rod dystrophy, Leber congenital amaurosis AD/AR 18 214
KCNV2 Retinal cone dystrophy AR 13 87
MERTK Retinitis pigmentosa AR 18 59
PDE6C Cone dystrophy AR 18 33
PDE6H Retinal cone dystrophy, Achromatopsia AD/AR 2 2
PROM1 Stargardt disease, Retinitis pigmentosa, Cone rod dystrophy, Macular dystrophy, retinal, AD/AR 10 58
PRPH2 Choriodal dystrophy, central areolar, Macular dystrophy, vitelliform, Retinitis pigmentosa, Retinitis punctata albescens, Macula dystrophy, patterned AD/Digenic 28 157
RAX2 Cone rod dystrophy AD 5 4
RDH5 Fundus albipunctatus AR 11 50
RPGR Retinitis pigmentosa XL 41 184
RPGRIP1 Cone rod dystrophy, Leber congenital amaurosis AR 23 117
SEMA4A Retinitis pigmentosa, Cone rod dystrophy AR 2 13

*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.

Gene Genomic location HG19 HGVS RefSeq RS-number Comment Reference
ABCA4 Chr1:94576926 c.302+68C>T NM_000350.2 rs761188244
ABCA4 Chr1:94493073 c.4539+1928C>T NM_000350.2
ABCA4 Chr1:94493000 c.4539+2001G>A NM_000350.2
ABCA4 Chr1:94492973 c.4539+2028C>T NM_000350.2 rs869320785
ABCA4 Chr1:94484082 c.5196+1056A>G NM_000350.2
ABCA4 Chr1:94484001 c.5196+1137G>A NM_000350.2 rs778234759
ABCA4 Chr1:94484001 c.5196+1137G>T NM_000350.2
GNAT2 Chr1:110151229 c.461+24G>A NM_005272.3 rs397515384
PROM1 Chr4:15989860 c.2077-521A>G NM_006017.2 rs796051882

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist

 

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.

 

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)

 

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Cone Rod Dystrophy Panel that covers classical genes associated with cone rod dystrophy, Jalili syndrome and Stargardt disease. 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.

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. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. 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.

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.

Find more info in Support

Choose an analysis method

$ $ 1700
$ $ 1000
$ $ 1900
Total $
Order now

ICD & CPT codes

CPT codes

SEQ 81434
DEL/DUP 81479


ICD codes

Commonly used ICD-10 codes when ordering the Cone Rod Dystrophy Panel

ICD-10 Disease
H35.50 Cone rod 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.

Subscribe to our newsletter