title: Genotype and phenotype of 101 dutch patients with congenital stationary night blindness.
abstract: OBJECTIVE
  To investigate the relative frequency of the genetic causes of the Schubert-Bornschein type of congenital stationary night blindness (CSNB) and to determine the genotype-phenotype correlations in CSNB1 and CSNB2.
  
  
  METHODS
  Clinic-based, longitudinal, multicenter study.
  
  
  METHODS
  A total of 39 patients with CSNB1 from 29 families and 62 patients with CSNB2 from 43 families.
  
  
  METHODS
  Patients underwent full ophthalmologic and electrophysiologic examinations. On the basis of standard electroretinograms (ERGs), patients were diagnosed with CSNB1 or CSNB2. Molecular analysis was performed by direct Sanger sequencing of the entire coding regions in NYX, TRPM1, GRM6, and GPR179 in patients with CSNB1 and CACNA1F and CABP4 in patients with CSNB2.
  
  
  METHODS
  Data included genetic cause of CSNB, refractive error, visual acuity, nystagmus, strabismus, night blindness, photophobia, color vision, dark adaptation (DA) curve, and standard ERGs.
  
  
  RESULTS
  A diagnosis of CSNB1 or CSNB2 was based on standard ERGs. The photopic ERG was the most specific criterion to distinguish between CSNB1 and CSNB2 because it showed a "square-wave" appearance in CSNB1 and a decreased b-wave in CSNB2. Mutations causing CSNB1 were found in NYX (20 patients, 13 families), TRPM1 (10 patients, 9 families), GRM6 (4 patients, 3 families), and GPR179 (2 patients, 1 family). Congenital stationary night blindness 2 was primarily caused by mutations in CACNA1F (55 patients, 37 families). Only 3 patients had causative mutations in CABP4 (2 families). Patients with CSNB1 mainly had rod-related problems, and patients with CSNB2 had rod- and cone-related problems. The visual acuity on average was better in CSNB1 (0.30 logarithm of the minimum angle of resolution [logMAR]) than in CSNB2 (0.52 logMAR). All patients with CSNB1 and only 54% of the patients with CSNB2 reported night blindness. The dark-adapted threshold was on average more elevated in CSNB1 (3.0 log) than in CSNB2 (1.8 log). The 3 patients with CABP4 had a relative low visual acuity, were hyperopic, had severe nonspecific color vision defects, and had only 1.0 log elevated DA threshold.
  
  
  CONCLUSIONS
  Congenital stationary night blindness 1, despite different causative mutations, shows 1 unique CSNB1 phenotype. Congenital stationary night blindness 2 caused by mutations in CABP4 merely shows cone-related problems and therefore appears to be distinct from CSNB2 caused by mutations in CACNA1F.
  
  
  BACKGROUND
  The author(s) have no proprietary or commercial interest in any materials discussed in this article.
authors.affiliation: Bartiméus Institute for the Visually Impaired, Zeist, The Netherlands; MOVE Research Institute, Faculty of Human Movement Sciences, VU University, Amsterdam, The Netherlands. Electronic address: miekebijveld@gmail.com.
authors.forename: Mieke M C
authors.initials: MM
authors.lastname: Bijveld
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Maarten
authors.initials: M
authors.lastname: Kamermans
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Prick
authors.forename: Frans C C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: Astrid M L
authors.initials: AM
authors.lastname: Kappers
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009216:Myopia / Q000235:genetics* / Q000503:physiopathology; D009426:Netherlands; D009755:Night Blindness / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D012030:Refractive Errors; D012684:Sensory Thresholds / Q000502:physiology; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: D005136:Eye Proteins