title: Mutation analysis of 3 genes in patients with Leber congenital amaurosis.
abstract: OBJECTIVE
  To assess the frequency of mutations in the CRX, GUCY2D, and RPE65 genes in patients with Leber congenital amaurosis (LCA).
  
  
  METHODS
  One hundred seventy-six probands with a clinical diagnosis of LCA were from 9 countries, with the largest subgroup being 39 probands from India.
  
  
  METHODS
  Samples were screened with single-strand conformation polymorphism analysis followed by DNA sequencing of 3 genes (CRX, GUCY2D, and RPE65) known to be associated with LCA.
  
  
  RESULTS
  Of the 176 probands, 28 (15.9%) harbored possible disease-causing mutations. The relative contribution of each gene to the total number of mutations was as follows: CRX, 2.8%; GUCY2D, 6.3%; and RPE65, 6.8%. No patients who harbored mutations in these genes had associated systemic abnormalities. Molecular diagnosis allowed definitive genetic counseling in a family affected with Best disease and LCA.
  
  
  CONCLUSIONS
  Molecular diagnosis may be of benefit to patients affected with LCA. The relative paucity of mutations found in this study suggests that more LCA-associated genes remain to be discovered.
  
  
  CONCLUSIONS
  Molecular diagnosis can confirm and clarify the diagnosis of LCA. As genotype data accumulate, clinical phenotypes associated with specific mutations will be established. This will facilitate the counseling of patients on their visual prognosis and the likelihood of associated systemic anomalies.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, Iowa City, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Lotery
authors.forename: P
authors.initials: P
authors.lastname: Namperumalsamy
authors.forename: S G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: R G
authors.initials: RG
authors.lastname: Weleber
authors.forename: G A
authors.initials: GA
authors.lastname: Fishman
authors.forename: M A
authors.initials: MA
authors.lastname: Musarella
authors.forename: C S
authors.initials: CS
authors.lastname: Hoyt
authors.forename: E
authors.initials: E
authors.lastname: Héon
authors.forename: A
authors.initials: A
authors.lastname: Levin
authors.forename: J
authors.initials: J
authors.lastname: Jan
authors.forename: B
authors.initials: B
authors.lastname: Lam
authors.forename: R E
authors.initials: RE
authors.lastname: Carr
authors.forename: A
authors.initials: A
authors.lastname: Franklin
authors.forename: S
authors.initials: S
authors.lastname: Radha
authors.forename: J L
authors.initials: JL
authors.lastname: Andorf
authors.forename: V C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: E M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D000293:Adolescent; D000328:Adult; D001766:Blindness / Q000151:congenital / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005817:Genetic Counseling; D006162:Guanylate Cyclase / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D015418:Optic Atrophies, Hereditary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D018807:Polymorphism, Single-Stranded Conformational; D011506:Proteins / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D002352:Carrier Proteins; D004247:DNA; D005136:Eye Proteins; D006162:Guanylate Cyclase; D018398:Homeodomain Proteins; D011506:Proteins; D015534:Trans-Activators; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C109288:cone rod homeobox protein