title: Non-invasive anterior segment and posterior segment optical coherence tomography and phenotypic characterization of aniridia.
abstract: OBJECTIVE
  To determine the value of optical coherence tomography (OCT) as a diagnostic tool in the critical evaluation of phenotypic variability seen in an aniridia family with a novel PAX6 mutation.
  
  
  METHODS
  Genetic and observational family study.
  
  
  METHODS
  Three-generation family segregating autosomal dominant aniridia.
  
  
  METHODS
  Ophthalmic examination included best-corrected visual acuity, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, tonometry, and OCT. PAX6 gene mutation analysis was carried out by direct sequencing of gene-specific PCR products and protein analysis by Western blot.
  
  
  RESULTS
  Intrafamilial variable expressivity was seen between 4 affected family members. Phenotype differences between twin children suggested that this was due to modifier gene effects rather than environment. Anterior segment OCT demonstrated a range of iridocorneal angle abnormalities and corneal thickening in only 3, but ciliary body hypoplasia in all 4 affected patients. Posterior segment OCT demonstrated dome-shaped, hypoplastic macular profiles in the 2 affected children. Novel outer retinal changes were also seen, suggestive of a phototoxic retinopathy not previously recognized in aniridia. Ocular disease segregated with a novel PAX6 Q178X nonsense mutation with Western blot analysis suggesting that this led to haploinsufficiency of PAX6 protein.
  
  
  CONCLUSIONS
  Non-contact OCT imaging allowed for a more detailed assessment of anterior and posterior segment disease in children and adults with aniridia plus nystagmus. This led to the identification of novel features and highlights a practical, non-contact strategy well suited to genotype/phenotype studies and the longitudinal management of aniridic glaucoma in children.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gregory-Evans
authors.forename: Richard
authors.initials: R
authors.lastname: Cheong-Leen
authors.forename: Sheena M
authors.initials: SM
authors.lastname: George
authors.forename: Judy
authors.initials: J
authors.lastname: Xie
authors.forename: Mariya
authors.initials: M
authors.lastname: Moosajee
authors.forename: Patricio
authors.initials: P
authors.lastname: Colapinto
authors.forename: Cheryl Y
authors.initials: CY
authors.lastname: Gregory-Evans
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D015783:Aniridia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D000869:Anterior Eye Segment / Q000473:pathology*; D001483:Base Sequence; D015153:Blotting, Western; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D004200:Diseases in Twins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008027:Light / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009887:Ophthalmoscopy; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D057972:Posterior Eye Segment / Q000473:pathology*; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology; D012097:Repressor Proteins / Q000235:genetics*; D012160:Retina / Q000528:radiation effects; D041623:Tomography, Optical Coherence; D014065:Tonometry, Ocular; D014429:Twins, Dizygotic / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology
chemical_list: D018389:Codon, Nonsense; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins