title: CRB1 gene mutations are associated with keratoconus in patients with leber congenital amaurosis.
abstract: OBJECTIVE
  To present an association of mutations in the CRB1 gene with keratoconus in patients with Leber congenital amaurosis (LCA).
  
  
  METHODS
  Sixteen patients with genotyped LCA (having the CRB1, CRX, RetGC, RPE65, and AIPL1 mutations) were recruited from one ophthalmology practice and examined for the presence of keratoconus. Corneal topography, visual acuity, and slit lamp biomicroscopic examination were performed in all cases.
  
  
  RESULTS
  The mean age of the patients was 34.5 years (range, 13-74). Visual acuities ranged from 20/40 to light perception. Corneal topography was successfully collected in 15 of the cases. Five of the 16 cases had slit lamp and/or topographic features consistent with keratoconus. One patient had a clinical picture that was keratoglobus-like. Of these six cases, four had a CRB1 mutation and two had a CRX mutation. Of the three subjects with the CRX mutation, one had keratoconus, one had the keratoglobus-like presentation, and one was normal. Our cohort represents 14 separate, unrelated families. Only one family comprised multiple members with LCA. These were three affected brothers, one with keratoconus, all with CRB1 mutations.
  
  
  CONCLUSIONS
  Although the results cannot exclude other gene mutations, they suggest that LCA patients with a CRB1 mutation may have a particular susceptibility to keratoconus.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois 60612, USA. timomcma@uic.edu
authors.forename: Timothy T
authors.initials: TT
authors.lastname: McMahon
authors.forename: Linda S
authors.initials: LS
authors.lastname: Kim
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Fishman
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Xinping C
authors.initials: XC
authors.lastname: Zhao
authors.forename: Richard W
authors.initials: RW
authors.lastname: Yee
authors.forename: Jarema
authors.initials: J
authors.lastname: Malicki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D001766:Blindness / Q000151:congenital / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D019781:Corneal Topography; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007640:Keratoconus / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D011956:Receptors, Cell Surface / Q000235:genetics; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D018398:Homeodomain Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D015534:Trans-Activators; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C403625:AIPL1 protein, human; C448939:CRB1 protein, human; C109288:cone rod homeobox protein; C110715:guanylate cyclase 1