X-Linked Complete Congenital Stationary Night Blindness (CSNB1) via the NYX Gene

X-linked congenital stationary night blindness (CSNB) is a non-progressive (stationary) inherited retinal disorder and has two clinical types, complete (CSNB1) and incomplete (CSNB2) (Rozzo et al. 1999). CSNB1 lacks rod function by electroretinography and dark adaptometry and refraction ranges from mild to severe myopia. CSNB2 shows some rod function on scotopic testing and refraction ranges from moderate hyperopia to moderate myopia (Musarella et al. 1989). Female carriers are usually asymptomatic (Musarella et al. 1989). However, a few cases of affected females in X-linked CSNB have been reported, most likely due to skewed X-inactivation (Ruttum et al. 1992).

Mutations in the NYX gene, which encodes glycosylphosphatidyl (GPI)-anchored protein called nyctalopin has been reported to be causative for CSNB1. Nyctalopin is a unique member of the leucine-rich proteoglycan family, which has shown to be expressed in both retina and kidney and may function as an adhesion molecule in the formation of synapses between neurons for the development of retinal interconnections (Bech-Hansen et al. 2000). So far, over 60 causative variants (missense, nonsense, splicing, small as well as gross deletions and duplications, complex genomic rearrangements) have been reported in this gene (Human Gene Mutation Database). A common NYX founder mutation c.855delG (p.Asp286Thrfs *62) has been reported in Flemish (population from Belgium) CSNB1 patients (Leroy et al. 2009).

Mutation screening in a total of 39 patients with CSNB1 from 29 families, detected NYX, TRPM1, GRM6 and GPR179 mutations in ~50% (20 patients, 13 families), ~25% (10 patients, 9 families), ~10% (4 patients, 3 families), and ~5% (2 patients, 1 family) of the patients, respectively (Bijveld et al. 2013). In an additional report, NYX mutations are reported to be a common cause of CSNB1 (Wang 2012).

This test provides full coverage of all coding exons of the NYX 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).