title: A phenotype-genotype correlation study of X-linked retinoschisis.
abstract: OBJECTIVE
  To compare the clinical phenotype and detailed electroretinographic parameters in X-linked retinoschisis (XLRS).
  
  
  METHODS
  Retrospective, comparative study.
  
  
  METHODS
  Fifty-seven patients (aged 1-67 years) with molecularly confirmed XLRS were clinically ascertained.
  
  
  METHODS
  Pattern electroretinography (PERG) and full-field electroretinography (ERG), incorporating international standard recordings, were performed in 44 cases. Thirteen patients, mostly pediatric, were tested using a simplified ERG protocol. On-Off and S-cone ERGs were performed in most adults. Fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) were available in 17 and 21 cases, respectively.
  
  
  METHODS
  The clinical and electrophysiologic data associated with different types of mutation in the RS1 gene.
  
  
  RESULTS
  Forty-three patients had missense changes (group A), and 14 patients had nonsense, splice-site, or frame-shifting mutations in the RS1 gene (group B). The mean best-corrected visual acuity was better in group A than in group B (0.34 and 0.21, respectively). Fundus examination revealed foveal schisis in approximately half of both groups. The bright-flash dark-adapted (DA) ERG (11.0 candela.sec.m(-2)) waveform was electronegative in 62% of group A eyes and 100% of group B eyes. The photopic 30-Hz flicker ERG was delayed in all group B eyes and all except 6 group A eyes. On-Off ERG b-waves were subnormal in 39% of group A and 89% of group B eyes; d-waves were delayed in 14 eyes (group A = 10, group B = 4). S-cone ERGs were abnormal in 50% of both groups. The PERG was abnormal in 88% of group A and 100% of group B eyes. A spoke-wheel pattern of high and low intensity was the most common FAF abnormality observed. The OCT showed intraretinal schitic cavities in the majority of eyes.
  
  
  CONCLUSIONS
  There is profound phenotypic variability in patients with XLRS. Most patients have DA bright-flash ERGs with a low b:a ratio in keeping with inner retinal dysfunction. Generalized cone system dysfunction is common and associated with an abnormal On-response and less frequent additional Off-response involvement. Nonsense, splice-site, or frame-shifting mutations in RS1 consistently caused electronegative bright-flash ERG, delayed flicker response, and abnormal PERG; missense mutations result in a wider range of ERG abnormalities.
authors: Moorfields Eye Hospital, City Road, London, United Kingdom.
authors: Ajoy
authors: A
authors: Vincent
authors: Anthony G
authors: AG
authors: Robson
authors: Magella M
authors: MM
authors: Neveu
authors: Genevieve A
authors: GA
authors: Wright
authors: Anthony T
authors: AT
authors: Moore
authors: Andrew R
authors: AR
authors: Webster
authors: Graham E
authors: GE
authors: Holder
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D003623:Dark Adaptation; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D010775:Photic Stimulation; D012160:Retina / Q000503:physiopathology*; D041441:Retinoschisis / Q000235:genetics* / Q000503:physiopathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D005136:Eye Proteins; C108726:RS1 protein, human