Cone-Rod Dystrophy (CORDX3) via the CACNA1F Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
Order Kits

NextGen Sequencing

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
4111 CACNA1F$640.00 81479 Add to Order
Pricing Comments

Our most cost-effective testing approach is NextGen sequencing with Sanger sequencing supplemented as needed to ensure sufficient coverage and to confirm NextGen calls that are pathogenic, likely pathogenic or of uncertain significance. If, however, full gene Sanger sequencing only is desired (for purposes of insurance billing or STAT turnaround time for example), please see link below for Test Code, pricing, and turnaround time information.

For Sanger Sequencing click here.
Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Sensitivity

Approximately 55% of X-Linked Congenital Stationary Night Blindness cases are due to mutations in CACNA1F gene (CSNB2) and the rest (45%) are caused by mutations in the NYX gene (CSNB1) (Boycott et al. 1993). Exome sequencing of 47 Chinese families with CORD identified CACNA1F mutations in ~2% (1/47) of their patient population (Huang et al. 2013).

See More

See Less

Del/Dup via aCGH

Test Code Test Copy GenesPriceCPT Code Copy CPT Codes
600 CACNA1F$990.00 81479 Add to Order
Pricing Comments

# of Genes Ordered

Total Price









Over 100

Call for quote

Targeted Testing

For ordering sequencing of targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features

Cone-rod dystrophy (CORD/CRD) is a rare hereditary retinal disorder with a worldwide prevalence of ~1 in 40,000. CRD is characterized by dysfunction or degeneration of cone photoreceptors with relative preservation of rod function in the initial stages. The most common symptoms are photophobia and epiphora in bright light, decreased visual acuity, and dyschromatopsia. Fundus changes may vary from mild pigment granularity to a distinct atrophic lesion in the central macula. As the disease progresses, degeneration of rod photoreceptors also occurs and leads to progressive night blindness and peripheral visual field loss (Hamel 2007). Incomplete X-linked congenital stationary night blindness (CSNB2) is a recessive, non-progressive (stationary) retinal disorder characterized by night blindness moderate myopia, nystagmus, strabismus and electroretinogram abnormalities of the Schubert-Bornschein type. Female carriers usually do not show any clinical signs. (Wutz et al. 2002; Bech-Hansen et al. 1998; Boycott et al. 1993). Aland Island eye disease (AIED), also known as Forsius-Eriksson ocular albinism, is an X-linked recessive retinal disease characterized by reduced visual acuity, mild red-green colour blindness, nystagmus, fundus hypopigmentation and foveal hypoplasia, astigmatism and progressive myopia. AIED symptoms have similarities with Ocular Albinism type 1. However, there is no misrouting of optic nerve fibers in AIED. Female carries may exhibit latent nystagmus and high myopia (Hawksworth et al. 1995; Jalkanen et al. 2007).


Non syndromic CRD is genetically heterogeneous and exhibits autosomal dominant (ad), autosomal recessive (ar) and, rarely, X-linked (xl) inheritance (Hamel 2007). So far about 25 genes have been implicated in different forms of CRD (RetNet). One of the xl-CRD (CORDX3) causative genes, CACNA1F, encodes retina-specific voltage-dependent calcium channel alpha 1F subunit (Cav1.4) and is localized to the Xp11.23 region. CACNA1F is also responsible for CSNB2 and AIED (Jalkanen 2006; Doering et al. 2007). Clinically, CORDX3 and CSNB2 have some overlapping clinical features such as the range of visual acuities, myopic refraction, and the ERG abnormalities. However, they are distinguishable from each other in some cases. For instance, CORDX3 is progressive, has onset between 3 and 33 years, has no congenital nystagmus or hyperopic refraction, and has only low grade astigmatism (Jalkanen 2006). In contrast, CSNB2 is stationary, in severe cases is seen early in life, and congenital nystagmus, hyperopic refraction, and astigmatism can be seen. AIED and CSNB2 also have some overlapping phenotypes but AIED has some additional features such as progressive myopia, dyschromatopsia, iris trans-illumination defects, and foveal hypoplasia (Vincent et al. 2011). Retina-specific CACNA1F is shown to have a specific functional role in visual processing (Naylor et al. 2000). Mouse mutant studies have shown that Cav1.4 calcium channel is crucial for the synaptic transmission at photoreceptor ribbon synapses (Morgans 2001). There are about hundred pathogenic variations in CACNA1F, which are associated with X-linked CORDX3, CSNB2 and AIED (Human Gene Mutation Database). A founder mutation in exon 27 of CACNA1F (c.3166dupC; p.Leu1056Profs*11) was identified Sixty-six male patients from 15 families of Mennonite ancestry (Boycott et al. 2000). A CACNA1F mutation screening in a large Finnish family (seven affected males, 10 carrier females, and 33 unaffected family members) identified a splice site variant, which co-segregated with the disease phenotype and not found in 200 control chromosomes (Jalkanen 2006). While gross deletions have also been reported, the percentage of cases due to gross deletions is unknown at this time (Human Gene Mutation Database).

Testing Strategy

For this NextGen test, the full coding regions plus ~10 bp of non-coding DNA flanking each exon are sequenced for the gene listed below. Sequencing is accomplished by capturing specific regions with an optimized solution-based hybridization kit, followed by massively parallel sequencing of the captured DNA fragments. Additional Sanger sequencing is performed for any regions not captured or with insufficient number of sequence reads. All pathogenic, likely pathogenic, or variants of uncertain significance are confirmed by Sanger sequencing.

Indications for Test

All patients with symptoms suggestive of CORDX3, CSNB2 and AIED, and apparent X-linked inheritance.


Official Gene Symbol OMIM ID
CACNA1F 300110
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Autism Spectrum Disorders and Intellectual Disability (ASD-ID) Comprehensive Sequencing Panel with CNV Detection
Congenital Stationary Night Blindness Sequencing Panel with CNV Detection
Retinitis Pigmentosa (includes RPGR ORF15) Sequencing Panel with CNV Detection


Genetic Counselors
  • Bech-Hansen NT, Naylor MJ, Maybaum TA, Pearce WG, Koop B, Fishman GA, Mets M, Musarella MA, Boycott KM. 1998. Loss-of-function mutations in a calcium-channel alpha1-subunit gene in Xp11.23 cause incomplete X-linked congenital stationary night blindness. Nat. Genet. 19: 264–267. PubMed ID: 9662400
  • Boycott KM, Pearce WG, Bech-Hansen NT. 2000. Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F. Can. J. Ophthalmol. 35: 204–213. PubMed ID: 10900517
  • Boycott KM, Sauvé Y, MacDonald IM. 1993. X-Linked Congenital Stationary Night Blindness. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301423
  • Doering CJ, Peloquin JB, McRory JE. 2007. The Cav1. 4 calcium channel: more than meets the eye. Channels 1: 4–11. PubMed ID: 19151588
  • Hamel CP. 2007. Cone rod dystrophies. Orphanet J Rare Dis 1;2:7. PubMed ID: 17270046
  • Hawksworth NR, Headland S, Good P, Thomas NS, Clarke A. 1995. Aland island eye disease: clinical and electrophysiological studies of a Welsh family. Br J Ophthalmol 79: 424–430. PubMed ID: 7612552
  • Huang L, Zhang Q, Li S, Guan L, Xiao X, Zhang J, Jia X, Sun W, Zhu Z, Gao Y, Yin Y, Wang P, et al. 2013. Exome Sequencing of 47 Chinese Families with Cone-Rod Dystrophy: Mutations in 25 Known Causative Genes. PLoS ONE 8: e65546. PubMed ID: 23776498
  • Human Gene Mutation Database (Bio-base).
  • Jalkanen R, Bech-Hansen NT, Tobias R, Sankila E-M, Mantyjarvi M, Forsius H, Chapelle A de la, Alitalo T. 2007. A Novel CACNA1F Gene Mutation Causes Aland Island Eye Disease. Investigative Ophthalmology & Visual Science 48: 2498–2502. PubMed ID: 17525176
  • Jalkanen R. 2006. X linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene. Journal of Medical Genetics 43: 699–704. PubMed ID: 16505158
  • Morgans CW. 2001. Localization of the α1F calcium channel subunit in the rat retina. Investigative ophthalmology & visual science 42: 2414–2418. PubMed ID: 11527958
  • Naylor MJ, Rancourt DE, Bech-Hansen NT. 2000. Isolation and characterization of a calcium channel gene, Cacna1f, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness. Genomics 66: 324–327. PubMed ID: 10873387
  • Vincent A, Wright T, Day MA, Westall CA, Héon E. 2011. A novel p. Gly603Arg mutation in CACNA1F causes \AAland island eye disease and incomplete congenital stationary night blindness phenotypes in a family. Molecular vision 17: 3262. PubMed ID: 22194652
  • Wutz K, Sauer C, Zrenner E, Lorenz B, Alitalo T, Broghammer M, Hergersberg M, Chapelle A de L, Weber BHF, Wissinger B, Meindl A, Pusch CM. 2002. Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling in mouse retina. European Journal of Human Genetics 10: 449–456. PubMed ID: 12111638
Order Kits

NextGen Sequencing using PG-Select Capture Probes

Test Procedure

We use a combination of Next Generation Sequencing (NGS) and Sanger sequencing technologies to cover the full coding regions of the listed genes plus ~10 bases of non-coding DNA flanking each exon.  As required, genomic DNA is extracted from the patient specimen.  For NGS, patient DNA corresponding to these regions is captured using an optimized set of DNA hybridization probes.  Captured DNA is sequenced using Illumina’s Reversible Dye Terminator (RDT) platform (Illumina, San Diego, CA, USA).  Regions with insufficient coverage by NGS are often covered by Sanger sequencing.

For Sanger sequencing, Polymerase Chain Reaction (PCR) is used to amplify targeted regions.  After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Patient DNA sequence is aligned to the genomic reference sequence for the indicated gene region(s). All differences from the reference sequences (sequence variants) are assigned to one of five interpretation categories, listed below, per ACMG Guidelines (Richards et al. 2015).

(1) Pathogenic Variants
(2) Likely Pathogenic Variants
(3) Variants of Uncertain Significance
(4) Likely Benign Variants
(5) Benign Variants

Human Genome Variation Society (HGVS) recommendations are used to describe sequence variants (  Rare variants and undocumented variants are nearly always classified as likely benign if there is no indication that they alter protein sequence or disrupt splicing.

Analytical Validity

As of March 2016, 6.36 Mb of sequence (83 genes, 1557 exons) generated in our lab was compared between Sanger and NextGen methodologies. We detected no differences between the two methods. The comparison involved 6400 total sequence variants (differences from the reference sequences). Of these, 6144 were nucleotide substitutions and 256 were insertions or deletions. About 65% of the variants were heterozygous and 35% homozygous. The insertions and deletions ranged in length from 1 to over 100 nucleotides.

In silico validation of insertions and deletions in 20 replicates of 5 genes was also performed. The validation included insertions and deletions of lengths between 1 and 100 nucleotides. Insertions tested in silico: 2200 between 1 and 5 nucleotides, 625 between 6 and 10 nucleotides, 29 between 11 and 20 nucleotides, 25 between 21 and 49 nucleotides, and 23 at or greater than 50 nucleotides, with the largest at 98 nucleotides. All insertions were detected. Deletions tested in silico: 1813 between 1 and 5 nucleotides, 97 between 6 and 10 nucleotides, 32 between 11 and 20 nucleotides, 20 between 21 and 49 nucleotides, and 39 at or greater than 50 nucleotides, with the largest at 96 nucleotides. All deletions less than 50 nucleotides in length were detected, 13 greater than 50 nucleotides in length were missed. Our standard NextGen sequence variant calling algorithms are generally not capable of detecting insertions (duplications) or heterozygous deletions greater than 100 nucleotides. Large homozygous deletions appear to be detectable.   

Analytical Limitations

Interpretation of the test results is limited by the information that is currently available.  Better interpretation should be possible in the future as more data and knowledge about human genetics and this specific disorder are accumulated.

When Sanger sequencing does not reveal any difference from the reference sequence, or when a sequence variant is homozygous, we cannot be certain that we were able to detect both patient alleles.  Occasionally, a patient may carry an allele which does not amplify, due to a large deletion or insertion.   In these cases, the report will contain no information about the second allele.  Our Sanger and NGS Sequencing tests are generally not capable of detecting Copy Number Variants (CNVs).

We sequence all coding exons for each given transcript, plus ~10 bp of flanking non-coding DNA for each exon.  Test reports contain no information about other portions of the gene, such as regulatory domains, deep intronic regions or any currently uncharacterized alternative exons.

In most cases, we are unable to determine the phase of sequence variants.  In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants due to somatic mosaicism is limited.  Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR.

Unless otherwise indicated, DNA sequence data is obtained from a specific cell-type (usually leukocytes from whole blood).   Test reports contain no information about the DNA sequence in other cell-types.

We cannot be certain that the reference sequences are correct.

Rare, low probability interpretations of sequencing results, such as for example the occurrence of de novo mutations in recessive disorders, are generally not included in the reports.

We have confidence in our ability to track a specimen once it has been received by PreventionGenetics.  However, we take no responsibility for any specimen labeling errors that occur before the sample arrives at PreventionGenetics.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

Order Kits

Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
loading Loading... ×

Copy Text to Clipboard