title: Clinical, histologic, and ultrastructural features of the corneal dystrophy caused by the R124L mutation of the BIGH3 gene.
abstract: OBJECTIVE
  This study was designed to describe the clinical, histologic, and ultrastructural features of the corneal dystrophy associated with the R124L mutation of the BIGH3 gene.
  
  
  METHODS
  Retrospective clinical and histologic review of a new genetic mutation.
  
  
  METHODS
  Thirty-four patients from five unrelated French families with corneal dystrophy caused by the R124L mutation of the BIGH3 gene were studied at the clinical, histologic, and ultrastructural levels. Records of patients carrying this mutation were compared with those from three unrelated patients with corneal dystrophy of Bowman's layer (CDB) type 2 (R555Q mutation) and from three unrelated patients with classic corneal granular dystrophy (R555W mutation).
  
  
  METHODS
  The mutational genetic status of the BIGH3 gene was determined for each patient, and the histologic and ultrastructural data available after corneal graft were analyzed.
  
  
  METHODS
  Genomic DNA was extracted from peripheral blood leukocytes. Exons 4 and 12 of the BIGH3 gene were amplified by the polymerase chain reaction (PCR), and the PCR products were directly sequenced.
  
  
  RESULTS
  All 34 patients with the R124L mutation displayed the clinical, histologic, and electron microscopic features of the dystrophy previously described as a superficial variant of corneal granular dystrophy. Combining molecular genetics with clinical and histologic findings established a clear distinction between the R555Q and R555W dystrophies.
  
  
  CONCLUSIONS
  The R124L mutation of the BIGH3 gene is associated with specific clinical and morphologic criteria. This indicates that molecular studies are needed for an adequate classification of corneal dystrophies. All criteria are presently available to segregate the dystrophy caused by the R124L mutation (known as CDB1) from the dystrophy caused by the R555Q mutation (known as CDB2).
authors.affiliation: Department of Ophthalmology, Hotel-Dieu de Paris, Paris, France. pld66@iname.com
authors.forename: P
authors.initials: P
authors.lastname: Dighiero
authors.forename: S
authors.initials: S
authors.lastname: Valleix
authors.forename: F
authors.initials: F
authors.lastname: D'Hermies
authors.forename: S
authors.initials: S
authors.lastname: Drunat
authors.forename: P
authors.initials: P
authors.lastname: Ellies
authors.forename: M
authors.initials: M
authors.lastname: Savoldelli
authors.forename: Y
authors.initials: Y
authors.lastname: Pouliquen
authors.forename: M
authors.initials: M
authors.lastname: Delpech
authors.forename: J M
authors.initials: JM
authors.lastname: Legeais
authors.forename: G
authors.initials: G
authors.lastname: Renard
mesh_terms: D000328:Adult; D003315:Cornea / Q000648:ultrastructure*; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D016039:Corneal Transplantation / Q000473:pathology; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D016326:Extracellular Matrix Proteins; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000235:genetics*; D000099222:betaIG-H3 Protein
chemical_list: D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein