Congenital Stationary Night Blindness Panel

Congenital Stationary Night Blindness (CSNB) is a retinal condition with negative bright-flash dark-adapted electroretinogram response, and optic atrophy or dysplastic changes, or both, in the optic nerve head. Typical findings of CSNB include impaired night vision, no pigmentary retinopathy, full visual fields consistent with myopia and strabismus, which appear from early childhood and are nonprogressive (Heckenlively et al. 1983. PubMed ID: 6605090; Nakamura et al. 2001. PubMed ID: 11381068). Early stages of retinitis pigmentosa (RP) and CSNB are difficult to distinguish (Chen et al. 2010. IOVS meeting abstract).

Congenital Stationary Night Blindness (CSNB) is a clinically and genetically heterogeneous retinal disorder. Pathogenic variants in ~20 genes have been shown to be associated with CSNB (Zeitz et al. 2015. PubMed ID: 25307992; Bijveld et al. 2013. PubMed ID: 23714322). CSNB exhibits autosomal recessive (AR), dominant (AD) and X-linked inheritance (XL). AR forms of complete CSNB have been reported to be caused due to sequence variations in GRM6 (CSNB1B), TRPM1 (CSNB1C), SLC24A1 (CSNB1D), GPR179 (CSNB1E), CACNA2D4, SAG, GRK1 and CABP4 (CSNB2). AD forms of complete CSNB has been reported to be caused due to sequence variations in RHO (CSNBAD1), PDE6B (CSNBAD2), and GNAT1 (CSNBAD3) LRIT3 (CSNB1F). The XL form of incomplete CSNB is due to sequence variants in CACNA1F (CSNB2A) and NYX (CSNB1) (Nakamura et al. 2001. PubMed ID: 11381068; Dryja et al. 2005. PubMed ID: 15781871; Bijveld et al. 2013. PubMed ID: 23714322; Morimura et al. 1998. PubMed ID: 9501220; Morimura et al. 1998. PubMed ID: 9501220). Other retinal disorders such as RDH5-associated Fundus albipunctatus or RPE65-associated retinitis pigmentosa exhibit night blindness (Narfström et al. 1989. PubMed ID: 2804031). Missense, splicing, nonsense, small and gross deletions/duplications have been reported in these genes (Human Gene Mutation Database).

See individual gene test descriptions for information on molecular biology of gene products.

Mutation screening in 101 Dutch CSNB patients (72 families) for 6 CSNB-associated genes (NYX, TRPM1, GRM6, GPR179, CACNA1F and CABP4) identified pathogenic variants in 94 patients (93%) (Bijveld et al. 2013. PubMed ID: 23714322).

So far large deletions and duplications have been reported in CACNA2D4, CACNA1F, GPR179, GRK1, NYX, PDE6B, RHO, SAG, SLC24A1, TRPM1, CHM and RPE65 (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.7% coverage of all coding exons of the genes 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 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).