Leber Congenital Amaurosis and Retinitis Pigmentosa via the CRB1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 4961 | CRB1 | 81406 | 81406,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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
Leber congenital amaurosis (LCA, OMIM 613835) and retinitis pigmentosa (RP, OMIM 268000) are inherited degenerative diseases of the retina. LCA is characterized by bilateral congenital blindness. RP is characterized by night blindness, with age of onset varying from childhood to middle age, progressing to constriction of the peripheral visual field and, eventually, to loss of central vision. Several clinical features of LCA overlap with those of RP. These include attenuated retinal vessels, abnormal electroretinographic (ERG) findings, and a variable amount of retinal pigmentation (Perrault et al. Nat Genet 14:461-464, 1996; Daiger et al. Arch Ophthalmol 125:151-158, 2007; Gu et al. J Med Genet 36:705-707, 1999). Both LCA and RP are clinically and genetically heterogeneous.
Genetics
LCA is inherited as an autosomal recessive trait in the vast majority of patients, while RP is either sporadic or familial with various modes of Mendelian, mitochondrial, or digenic inheritance. To date, 14 genes have been implicated in LCA and 25 in autosomal recessive RP (AR-RP; den Hollander et al. Prog Retin Eye Res 27:391-419, 2008; Daiger et al. Arch Ophthalmol 125:151-158, 2007). The clinical overlap between LCA and RP is illustrated by the involvement of six genes in both conditions. These include the CRB1 gene. CRB1 variants were first identified in patients with a severe form of AR-RP characterized by preservation of the para-arteriolar retinal pigment epithelium (PPRPE) (RP12, OMIM 600105) (den Hollander et al. Nat Genet 23:217-221, 1999). Subsequently, CRB1 variants were reported in patients with LCA (Lotery et al. Arch Ophthalmol 119: 415-420, 2001). Over 40 different CRB1 variants have been reported in patients with LCA and 32 in RP. These variants include missense, nonsense, splicing, and small deletions/insertions. In addition to LCA and RP12, CRB1 variants were found in rare cases with severe AR-RP without PPRPE (Lotery et al. Ophthalmic Genet 22:163-169, 2001; Booij et al. J Med Genet 42:e67, 2005) and in one family with a history of autosomal dominant pigmented paravenous chorioretinal atrophy (PPCRA, OMIM 172870) (McKay et al. Invest Ophthalmol Vis Sci 46: 322-328, 2005). The CRB1 protein is expressed specifically in human retina and brain.
Clinical Sensitivity - Sequencing with CNV PG-Select
CRB1 variants account for ~ 15 % of patients with LCA (Yzer et al. Invest Ophthalmol Vis Sci 47:1167-1176, 2006), 6.5% of patients with AR-RP (Bernal et al. J Med Genet 40:e89, 2003) and up to 50% of patients with AR-RP and PPRPE (den Hollander et al. Hum Mutat 24:355-369, 2004).
Testing Strategy
This test provides full coverage of all coding exons of the CRB1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
All patients with LCA and with early-onset RP are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CRB1.
All patients with LCA and with early-onset RP are candidates. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in CRB1.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| CRB1 | 604210 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Leber Congenital Amaurosis 8 | 613835 | |
| Pigmented Paravenous Chorioretinal Atrophy | AD | 172870 |
| Retinitis Pigmentosa 12 | AR | 600105 |
Related Tests
| Name |
|---|
| Leber Congenital Amaurosis 4 (LCA4) via the AIPL1 Gene |
| Leber Congenital Amaurosis Panel |
| Retinitis Pigmentosa Panel |
Citations
- Bernal, S., et.al. (2003). "Study of the involvement of the RGR, CRPB1, and CRB1 genes in the pathogenesis of autosomal recessive retinitis pigmentosa." J Med Genet 40(7): e89. PubMed ID: 12843338
- Booij JC. 2005. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Journal of Medical Genetics 42: e67–e67. PubMed ID: 16272259
- Daiger et al. 2007. PubMed ID: 17296890
- 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
- den Hollander, A. I., et.al. (1999). "Mutations in a human homologue of Drosophila crumbs cause retinitis pigmentosa (RP12)." Nat Genet 23(2): 217-21. PubMed ID: 10508521
- den Hollander, A. I., et.al. (2004). "CRB1 mutation spectrum in inherited retinal dystrophies." Hum Mutat 24(5): 355-69. PubMed ID: 15459956
- Gu S. et al. 1999. Journal of Medical Genetics. 36: 705-7. PubMed ID: 10507729
- Lotery, A. J., et.al. (2001). "CRB1 mutations may result in retinitis pigmentosa without para-arteriolar RPE preservation." Ophthalmic Genet 22(3): 163-9. PubMed ID: 11559858
- Lotery, A. J., et.al. (2001). "Mutations in the CRB1 gene cause Leber congenital amaurosis." Arch Ophthalmol 119(3): 415-20. PubMed ID: 11231775
- McKay, G. J., et.al. (2005). "Pigmented paravenous chorioretinal atrophy is associated with a mutation within the crumbs homolog 1 (CRB1) gene." Invest Ophthalmol Vis Sci 46(1): 322-8. PubMed ID: 15623792
- Perrault I, Rozet JM, Calvas P, Gerber S, Camuzat A, Dollfus H, Châtelin S, Souied E, Ghazi I, Leowski C, Bonnemaison M, Paslier D Le, et al. 1996. Retinal-specific guanylate cyclase gene mutations in Leber’s congenital amaurosis. Nat. Genet. 14: 461–464. PubMed ID: 8944027
- Yzer, S., et.al. (2006). "Microarray-based mutation detection and phenotypic characterization of patients with Leber congenital amaurosis." Invest Ophthalmol Vis Sci 47(3): 1167-76. PubMed ID: 16505055
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
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