Leber Congenital Amaurosis via the CRX Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
665 CRX$490.00 81404 Add to Order
Targeted Testing

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

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity
This test allows the detection of mutations in approximately 2% of patients with LCA (Dharmaraj et al. Ophthalmic Genet 21:135-150, 2000).  Except for the R90W mutation, all CRX mutations are completely penetrant and cause disease in heterozygotes (Rivolta et al. Hum Mut 18:488-498, 2001). PreventionGenetics plans to offer Tests for all genes known to cause LCA, and is committed to add new tests as the remaining LCA genes are discovered.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CRX$990.00 81479 Add to Order
Pricing Comment

# of Genes Ordered

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Over 100

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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features
Nonsyndromic Leber Congenital Amaurosis (LCA, OMIM  613829) is a group of severe retinal dystrophies with early onset.  The clinical hallmarks are bilateral congenital blindness, a diminished or absent electroretinogram and high hyperopia.  Additional symptoms include nystagmus, photophobia, eye poking and sluggish pupils (Cremers et al. Hum Mol Genet 11:1169-1176, 2002).  LCA affects 3 per 100,000 newborn babies worldwide and has been described in various ethnic groups.  Patients with LCA represent ~ 5 % of all retinal dystrophies (Perrault et al. Mol Gen Metabol 68:200-208, 1999). Genetic abnormalities are the primary cause of LCA.
LCA represents the most common genetic cause of congenital visual impairments in infants and adolescents. It is usually inherited in an autosomal recessive manner, although in several families LCA is transmitted as an autosomal dominant trait (Rivolta et al. Hum Mut 18:488-498, 2001). Sporadic patients with LCA were also reported (Hanein et al. Hum Mut 23:306-317, 2004). LCA is genetically and clinically heterogeneous. Currently, mutations in fourteen (14) genes account for ~70% of all cases (den Hollander et al. Prog Retin Eye Res 27:391-419, 2008). These include the CRX gene. About thirteen different CRX mutations, distributed along the entire coding sequence, have been implicated in LCA. All causative CRX mutations were heterozygous and detected in patients with autosomal dominant or sporadic LCA, except for the R90W substitution. This mutation was reported in one patient from a consanguineous Indian family and showed a classical autosomal recessive pattern (Swaroop et al. Hum Mol Genet 8:299-305, 1999). In addition to LCA, CRX mutations were found in patients with autosomal dominant cone-rod dystrophy (AD-CRD, OMIM 120970); and one novel mutation (c.458delC) was reported in an Italian family with autosomal dominant Retinitis Pigmentosa (AD-RP, OMIM 268000) (Ziviello et al. J Med Genet 42:e47, 2005).  The CRX protein is a photoreceptor-specific transcription factor involved in the regulation of several photoreceptor specific genes.
Testing Strategy
This test involves bidirectional DNA sequencing of all 3 coding exons and splice sites of the CRX gene. The full coding sequence of each exon plus ~10 bp of flanking-coding DNA on either side are sequenced. We will also sequence any single exon (Test #100) or pair of exons (Test #200) in family members of patients with known mutations or to confirm research results.
Indications for Test
Familial cases with symptoms suggestive of LCA and autosomal dominant inheritance, patients with LCA from consanguineous Indian families and isolated cases of LCA. The CRX gene is also a candidate for patients with AD-CRD and patients with AD-RP.


Official Gene Symbol OMIM ID
CRX 602225
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Leber Congenital Amaurosis 1 (LCA1) and Cone-Rod dystrophy 6 (CORD6) via the GUCY2D Gene
Leber Congenital Amaurosis 4 (LCA4) via AIPL1 Gene Sequencing with CNV Detection
Leber Congenital Amaurosis Sequencing Panel with CNV Detection


Genetic Counselors
  • Cremers FP, Hurk JA van den, Hollander AI den. 2002. Molecular genetics of Leber congenital amaurosis. Human molecular genetics 11: 1169–1176. PubMed ID: 12015276
  • den Hollander AI, Roepman R, Koenekoop RK, Cremers FPM. 2008. Leber congenital amaurosis: genes, proteins and disease mechanisms. Prog Retin Eye Res 27: 391–419. PubMed ID: 18632300
  • Dharmaraj, S. R., (2000). "Mutational analysis and clinical correlation in Leber congenital amaurosis." Ophthalmic Genet 21(3): 135-50. PubMed ID: 11035546
  • Hanein, S., (2004). "Leber congenital amaurosis: comprehensive survey of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for molecular diagnosis." Hum Mutat 23(4): 306-317. PubMed ID: 15024725
  • Perrault I. et al. (1999). "Leber congenital amaurosis." Mol Genet Metab 68(2): 200-208. PubMed ID: 10527670
  • Rivolta, C. (2001). "Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX." Hum Mutat 18(6): 488-498. PubMed ID: 11748842
  • Swaroop, A., (1999). "Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function." Hum Mol Genet 8(2): 299-305. PubMed ID: 9931337
  • Ziviello, C., (2005). "Molecular genetics of autosomal dominant retinitis pigmentosa (ADRP): a comprehensive study of 43 Italian families." J Med Genet 42(7): e47. PubMed ID: 15994872
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all 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 for example 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 and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

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.
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