title: Ultrastructural and molecular analysis of Bowman's layer corneal dystrophies: an epithelial origin?
abstract: OBJECTIVE
  Two mutations (R555Q and R124L) in the BIGH3 gene have been described in anterior or Bowman's layer dystrophies (CDB). The clinical, molecular, and ultrastructural findings of five families with CDB was reviewed to determine whether there is a consistent genotype:phenotype correlation.
  
  
  METHODS
  Keratoplasty tissue from each patient was examined by light and electron microscopy (LM and EM). DNA was obtained, and exons 4 and 12 of BIGH3 were analyzed by polymerase chain reaction and single-stranded conformation polymorphism/heteroduplex analysis. Abnormally migrating products were analyzed by direct sequencing.
  
  
  RESULTS
  In two families with type I CDB (CDBI), the R124L mutation was defined. There were light and ultrastructural features of superficial granular dystrophy and atypical banding of the "rod-shaped bodies" ultrastructurally. Patients from three families with "honeycomb" dystrophy were found to carry the R555Q mutation and had characteristic features of Bowman's dystrophy type II (CDBII).
  
  
  CONCLUSIONS
  There is a strong genotype:phenotype correlation among CBDI (R124L) and CDBII (R555Q). LM and EM findings suggest that epithelial abnormalities may underlie the pathology of both conditions. The findings clarify the confusion over classification of the Bowman's layer dystrophies.
authors.affiliation: Department of Ophthalmology, Manchester Royal Eye Hospital, Manchester, United Kingdom.
authors.forename: A E
authors.initials: AE
authors.lastname: Ridgway
authors.forename: S
authors.initials: S
authors.lastname: Akhtar
authors.forename: F L
authors.initials: FL
authors.lastname: Munier
authors.forename: D F
authors.initials: DF
authors.lastname: Schorderet
authors.forename: H
authors.initials: H
authors.lastname: Stewart
authors.forename: R
authors.initials: R
authors.lastname: Perveen
authors.forename: R E
authors.initials: RE
authors.lastname: Bonshek
authors.forename: M T
authors.initials: MT
authors.lastname: Odenthal
authors.forename: M
authors.initials: M
authors.lastname: Dixon
authors.forename: R
authors.initials: R
authors.lastname: Barraquer
authors.forename: R
authors.initials: R
authors.lastname: Escoto
authors.forename: G C
authors.initials: GC
authors.lastname: Black
mesh_terms: D000328:Adult; D001485:Basement Membrane / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D019573:Epithelium, Corneal / Q000648:ultrastructure*; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007223:Infant; D015948:Keratoplasty, Penetrating / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014792:Visual Acuity; D000099222:betaIG-H3 Protein
chemical_list: D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein