title: Phenotypes in defined genotypes including siblings with Usher syndrome.
abstract: OBJECTIVE
  To characterize visual function in defined genotypes including siblings with Usher syndrome.
  
  
  METHODS
  Thirteen patients with phenotypically different subtypes of Usher syndrome, including 3 families with affected siblings, were selected. Genetic analysis and ophthalmological examinations including visual fields, full-field electroretinography (ERG), multifocal electroretinography (mf ERG), and optical coherence tomography (OCT) were assessed. The patients' degree of visual handicap was evaluated by a questionnaire (ADL).
  
  
  RESULTS
  Twelve of thirteen patients were genotyped as Usher 1B, 1D, 1F, 2A, 2C or 3A. In 12 of 13 patients examined with ERG the 30 Hz flickering light response revealed remaining cone function. In 3 of the patients with Usher type 1 mf ERG demonstrated a specific pattern, with a sharp distinction between the area with reduced function and the central area with remaining macular function and normal peak time. OCT demonstrated loss of foveal depression with distortion of the foveal architecture in the macula in all patients. The foveal thickness ranged from 159 to 384 µm and was not correlated to retinal function. Three siblings shared the same mutation for Usher 2C but in contrast to previous reports regarding this genotype, 1 of them diverged in phenotype with substantially normal visual fields, almost normal OCT and mf ERG findings, and only moderately reduced rod and cone function according to ERG.
  
  
  CONCLUSIONS
  Evaluation of visual function comprising both the severity of the rod cone degeneration and the function in the macular region confirm phenotypical heterogeneity within siblings and between different genotypes of Usher syndrome.
authors.affiliation: Department of Ophthalmology, Skåne University Hospital, Lund, Sweden. eva.malm@med.lu.se
authors.forename: Eva
authors.initials: E
authors.lastname: Malm
authors.forename: Vesna
authors.initials: V
authors.lastname: Ponjavic
authors.forename: Claes
authors.initials: C
authors.lastname: Möller
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: Sten
authors.initials: S
authors.lastname: Andréasson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics; D002648:Child; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009218:Myosins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D012160:Retina / Q000503:physiopathology; D035781:Siblings; D011795:Surveys and Questionnaires; D041623:Tomography, Optical Coherence; D052245:Usher Syndromes / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: C417525:ADGRV1 protein, human; C442480:CDH23 protein, human; C498835:CDHR15, human; C437067:CLRN1 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D016326:Extracellular Matrix Proteins; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; C112735:USH2A protein, human; D009218:Myosins