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Leber Congenital Amaurosis Panel

The Leber Congenital Amaurosis Panel is a comprehensive next-generation sequencing (NGS) panel that can be used to confirm a clinical diagnosis of Leber congenital amaurosis or identify at-risk individuals.

Leber congenital amaurosis is caused by dystrophy of the retina, and typically presents as severe vision loss either in the neonatal period or within the first year of life. In addition to vision loss, individuals may have nystagmus, absent pupillary responses, photophobia, hyperopia, and keratoconus. Leber congenital amaurosis may include only ocular manifestations or may be part of a syndromic condition. Vision loss is typically stable and usually does not progress with age.

Included Disorders

This panel includes genes associated with:

  • Leber congenital amaurosis
  • Cone-rod dystrophy
  • Retinitis pigmentosa
  • Senior-Loken syndrome
  • Vitelliform macular dystrophy
  • Klippel-Feil syndrome

Prevalence

The prevalence of Leber congenital amaurosis is between 1 in 30,000 to 1 in 50,000 individuals (PMID:20301475), but may be higher in certain populations.

Inheritance and Penetrance

Leber congenital amaurosis is typically inherited in an autosomal recessive manner, although it may be inherited in autosomal dominant fashion in rare cases (most frequently when caused by heterozygous mutations in CRX).

Clinical Sensitivity

Disease causing variants can be identified in approximately 50-70% of Leber congenital amaurosis cases (Chacon-camacho and Zenteno, 2015). The Leber Congenital Amaurosis Panel includes all of the common genetic causes related to this disease.

Methodology and Analytical Sensitivity

Next-generation sequencing technology is used to test clinically relevant portions of each gene, including coding exons, adjacent flanking bases, and selected introns/noncoding variants. Pathogenic and likely pathogenic variants are confirmed by orthogonal methods. Copy number variants, including intragenic deletions and duplications are detected to a resolution of a single exon. To request analysis of a specific single exon copy number variant, please contact our Client Services team prior to ordering. Analytical sensitivity and specificity of the assay is >99%.

Indications for Testing

  • Confirmation of a clinical diagnosis
  • Risk assessment for asymptomatic family members of proband with molecular diagnosis of Leber congenital amaurosis

Included genes (21)

AIPL1 CRB1 GUCY2D LCA5 NMNAT1 RD3 RPGRIP1
CABP4 CRX IQCB1 LRAT OTX2 RDH12 SPATA7
CEP290 GDF6 KCNJ13 MERTK PRPH2 RPE65 TULP1

 

Additions to the Leber Congenital Amaurosis Panel

Emerging evidence genes can also be added to the Leber Congenital Amaurosis Panel. These genes do not have a clear association with Leber congenital amaurosis, but emerging evidence suggests that they may play a role in disease pathogenesis.

Emerging Evidence Genes (4)

BBS4 DTHD1 IMPDH1 SNRNP200

 

References

  1. Weleber RG, Francis PJ, Trzupek KM, et al. Leber Congenital Amaurosis. 2004 Jul 7 [Updated 2013 May 2]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  2. 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.