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  • Test code: 05143
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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  1. Test Catalog
  2. Invitae Leber Congenital Amaurosis Panel

Invitae Leber Congenital Amaurosis Panel

Test description

The Invitae Leber Congenital Amaurosis Panel analyzes up to 21 genes associated with Leber congenital amaurosis (LCA), which is characterized by blindness or severe vision loss typically presenting in infancy. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for LCA.

Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

Genes tested

Primary panel

AIPL1 CEP290 CRB1 CRX GDF6 GUCY2D IQCB1 KCNJ13 LCA5 LRAT NMNAT1 OTX2 PRPH2 RD3 RDH12 RPE65 RPGRIP1 SPATA7 TULP1

Add-on Preliminary-evidence Genes for Leber Congenital Amaurosis

BBS4 IMPDH1

In addition to the primary panel, clinicians can also choose to include two genes that have preliminary evidence of association with Leber congenital amaurosis. At this time, the association of these two genes with Leber congenital amaurosis remains uncertain. However, some clinicians may wish to include genes that may prove to be clinically significant in the future. Visit our Preliminary-evidence genes page to learn more. These genes can be added at no additional charge.

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Primary panel (19 genes)

AIPL1 CEP290 CRB1 CRX GDF6 GUCY2D IQCB1 KCNJ13 LCA5 LRAT NMNAT1 OTX2 PRPH2 RD3 RDH12 RPE65 RPGRIP1 SPATA7 TULP1

Panel details and technical assay limitations
Add-on Preliminary-evidence Genes for Leber Congenital Amaurosis (2 genes)

In addition to the primary panel, clinicians can also choose to include two genes that have preliminary evidence of association with Leber congenital amaurosis. At this time, the association of these two genes with Leber congenital amaurosis remains uncertain. However, some clinicians may wish to include genes that may prove to be clinically significant in the future. Visit our Preliminary-evidence genes page to learn more. These genes can be added at no additional charge.

BBS4 IMPDH1

Panel details and technical assay limitations

Clinical information

  • Leber congenital amaurosis (LCA)

LCA is a group of early-onset retinal dystrophies characterized by severe and early vision loss (typically in infancy), absent or sluggish pupillary response, severely abnormal or absent ERG response and Franceschetti’s oculo-digital sign, which is a behavior consisting of eye poking, rubbing, and pressing. Additionally, many affected individuals also present with nystagmus, photophobia, high hyperopia and keratoconus.

Pathogenic variants in these 19 genes are estimated to account for at least 50–70% of cases of LCA.

LCA is most often inherited in an autosomal recessive manner. CRX, OTX2, and IMPDH1 are exceptions and are associated with autosomal dominant LCA.

Penetrance of LCA is generally expected to be high, however, reduced penetrance has been reported.

LCA occurs in 1 in 30,000 to 50,000 individuals.

Testing may be considered for individuals with infantile-onset blindness or severe visual impairment, extinguished or severely reduced scotopic and photopic electroretinogram (ERG), and/or Franceschetti’s oculo-digital sign, characterized by poking, rubbing, and/or pressing of the eyes.

  1. Chacon-Camacho, OF, Zenteno, JC. Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015; 3(2):112-24. PMID: 25685757
  2. Fazzi, E, et al. Leber's congenital amaurosis: an update. Eur. J. Paediatr. Neurol. 2003; 7(1):13-22. PMID: 12615170
  3. Perrault, I, et al. Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype. PLoS ONE. 2013; 8(1):e51622. PMID: 23308101
  4. Weleber, RG, et al. Leber Congenital Amaurosis. 2004 Jul 07. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301475
  5. Hedergott, A, et al. Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature. Graefes Arch. Clin. Exp. Ophthalmol. 2015; 253(12):2239-46. PMID: 26464178
  6. Siemiatkowska, AM, et al. Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1. JAMA Ophthalmol. 2014; 132(8):1002-4. PMID: 24830548

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
AIPL1 NM_014336.4
BBS4 NM_033028.4
CEP290* NM_025114.3
CRB1 NM_201253.2
CRX NM_000554.4
GDF6 NM_001001557.2
GUCY2D NM_000180.3
IMPDH1 NM_000883.3
IQCB1 NM_001023570.2
KCNJ13 NM_002242.4
LCA5 NM_181714.3
LRAT NM_004744.4
NMNAT1 NM_022787.3
OTX2 NM_172337.2
PRPH2 NM_000322.4
RD3 NM_183059.2
RDH12 NM_152443.2
RPE65 NM_000329.2
RPGRIP1 NM_020366.3
SPATA7 NM_018418.4
TULP1 NM_003322.4

CEP290: Analysis includes the intronic variant NM_025114.3:c.2991+1655A>G.

Clinical resources
Invitae brochure Ophthalmology gene list Pediatric genetics gene list
Patient resources
Patient guide: Genetic testing simplified
Test information
Forms page Specimen requirements page

References

  1. Chacon-Camacho, OF, Zenteno, JC. Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases. 2015; 3(2):112-24. PMID: 25685757
  2. Fazzi, E, et al. Leber's congenital amaurosis: an update. Eur. J. Paediatr. Neurol. 2003; 7(1):13-22. PMID: 12615170
  3. Hedergott, A, et al. Clinical and genetic findings in a family with NMNAT1-associated Leber congenital amaurosis: case report and review of the literature. Graefes Arch. Clin. Exp. Ophthalmol. 2015; 253(12):2239-46. PMID: 26464178
  4. Perrault, I, et al. Union makes strength: a worldwide collaborative genetic and clinical study to provide a comprehensive survey of RD3 mutations and delineate the associated phenotype. PLoS ONE. 2013; 8(1):e51622. PMID: 23308101
  5. Siemiatkowska, AM, et al. Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1. JAMA Ophthalmol. 2014; 132(8):1002-4. PMID: 24830548
  6. Weleber, RG, et al. Leber Congenital Amaurosis. 2004 Jul 07. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301475

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