Leber Congenital Amaurosis via the CRX Gene
Summary and Pricing 
Test Method
Exome Sequencing with CNV Detection
| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 9119 | CRX | 81404 | 81404,81479 | $990 | Order Options and Pricing |
Pricing Comments
Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).
Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).
The Sanger Sequencing method for this test is NY State approved.
For Sanger Sequencing click here.Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
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.
Genetics
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, variants in 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 13 different CRX variants, distributed along the entire coding sequence, have been implicated in LCA. All causative CRX variants were heterozygous and detected in patients with autosomal dominant or sporadic LCA, except for the p.R90W substitution. This variant 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 variants were found in patients with autosomal dominant cone-rod dystrophy (AD-CRD, OMIM 120970); and one novel variant (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.
Clinical Sensitivity - Sequencing with CNV PGxome
This test allows the detection of variants in approximately 2% of patients with LCA (Dharmaraj et al. Ophthalmic Genet 21:135-150, 2000). Except for the p.R90W variant, all CRX variants are completely penetrant and cause disease in heterozygotes (Rivolta et al. Hum Mut 18:488-498, 2001).
Testing Strategy
This test provides full coverage of all coding exons of the CRX gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).
Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).
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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CRX.
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. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CRX.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CRX | 602225 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Cone-Rod Dystrophy 2 | 120970 | |
| Leber Congenital Amaurosis 7 | 613829 |
Related Tests
| Name |
|---|
| Leber Congenital Amaurosis 4 (LCA4) via the AIPL1 Gene |
| Leber Congenital Amaurosis Panel |
Citations
- 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., et.al. (2000). "Mutational analysis and clinical correlation in Leber congenital amaurosis." Ophthalmic Genet 21(3): 135-50. PubMed ID: 11035546
- Hanein, S., et.al. (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. et.al. (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
- Rivolta, C. et.al. (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., et.al. (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., et.al. (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
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
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.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
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.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
PGxome (Exome) Sequencing Panel
PGnome (Genome) Sequencing Panel
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ORDER OPTIONS
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