title: Clinical outcome of eight BIGH3-linked corneal dystrophies.
abstract: OBJECTIVE
  To determine whether the mutational pattern of BIGH3-linked corneal dystrophies (CDs) can accurately predict the clinical course of the disease and be helpful in planning adequate surgical treatment.
  
  
  METHODS
  Retrospective noncomparative case series.
  
  
  METHODS
  Chart review of 73 patients (110 eyes) with recently confirmed BIGH3 mutations who underwent a penetrating keratoplasty (PK) from 1978 through 1999. Diagnoses included Thiel-Benhke CD (TBCD/R555Q) (13 eyes), classic granular CD (CGCD/R555W) (28 eyes), superficial variant of granular dystrophy (SVGD/R124 l) (27 eyes), lattice CD type I (LCDI/R124C) (20 eyes), Avellino CD (ACD/R124H) (2 eyes), H626R-lattice dystrophy (LCD/H626R) (6 eyes), and two novel dystrophies: a French variant of granular dystrophy (FVGD/R124 l+DT125-DE126) (9 eyes) and a French lattice CD type IIIA (LCDIIIA/A546T) (5 eyes).
  
  
  METHODS
  The mutation of the BIGH3 gene was characterized for all patients. Clinical data were reviewed for each patient, and included age at first PK and elapsed time before significant recurrence (as defined by a severe decrease in best-corrected visual acuity related to recurrent deposits in the graft).
  
  
  METHODS
  Mean age at first PK and delay before a significant recurrence.
  
  
  RESULTS
  Mutational pattern was highly correlated with the clinical course of each dystrophy. According to the genetic mutation, two groups with different prognosis were identified. Group 1 was defined by the presence of the FVGD/R124 l+DT125-DE126 and SVGD/R124 l mutations and was characterized by the early need for treatment and early recurrence of deposits. Group 2 was molecularly defined by the presence of any of the following mutations: LCDI/R124C, CGCD/R555W, LCDIIIA/A546T, TBCD/R555Q, and LCD/H626R. In group 2, mean age at first treatment was older, and delay before a significant recurrence was longer as compared with group 1 (P = 0.0001).
  
  
  CONCLUSIONS
  These results demonstrate that there is a direct correlation between the molecular defect and the clinical course of BIGH3-linked CDs. They also indicate that molecular characterization of the genetic defect will help predict and design adequate surgical treatment for patients with ambiguous clinical diagnosis.
authors.affiliation: Department of Ophthalmology, Hôpital Hôtel-Dieu de Paris, 1 Place du Parvis Notre-Dame, 75004 Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Ellies
authors.forename: Gilles
authors.initials: G
authors.lastname: Renard
authors.forename: Sophie
authors.initials: S
authors.lastname: Valleix
authors.forename: Pierre Yves
authors.initials: PY
authors.lastname: Boelle
authors.forename: Paul
authors.initials: P
authors.lastname: Dighiero
mesh_terms: D000328:Adult; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D004247:DNA / Q000032:analysis; D004252:DNA Mutational Analysis; D016326:Extracellular Matrix Proteins; D006801:Humans; D015948:Keratoplasty, Penetrating; D008875:Middle Aged; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014792:Visual Acuity; D000099222:betaIG-H3 Protein
chemical_list: D004247:DNA; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein