title: Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis.
abstract: OBJECTIVE
  To study the retinal degeneration in an 11 -year-old patient with Leber congenital amaurosis (LCA) caused by mutation in GUCY2D.
  
  
  METHODS
  Comparative human tissue study.
  
  
  METHODS
  Two subjects with LCA; postmortem eye from one LCA patient and three normal donors.
  
  
  METHODS
  Clinical and visual function studies were performed between the ages of 6 and 10 years in the LCA eye donor and at age 6 in an affected sibling. Genomic DNA was screened for mutations in known LCA genes. The retina of the 11 -year-old subject with LCA was compared with normal retinas from donors age 3 days, 18 years, and 53 years. The tissues were processed for histopathologic studies and immunofluorescence with retinal cell-specific antibodies.
  
  
  RESULTS
  Vision in both siblings at the ages examined was limited to severely impaired cone function. Mutation in the GUCY2D gene was identified in both siblings. Histopathologic study revealed rods and cones without outer segments in the macula and far periphery. The cones formed a monolayer of cell bodies, but the rods were clustered and had sprouted neurites in the periphery. Rods and cones were not identified in the midperipheral retina. The inner nuclear layer appeared normal in thickness throughout the retina, but ganglion cells were reduced in number.
  
  
  CONCLUSIONS
  An 11-year-old subject with LCA caused by mutant GUCY2D had only light perception but retained substantial numbers of cones and rods in the macula and far periphery. The finding of numerous photoreceptors at this age may portend well for therapies designed to restore vision at the photoreceptor level.
authors.affiliation: Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, 51 North 39th Street, Philadelphia, PA 19104, USA.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Milam
authors.forename: Mark R
authors.initials: MR
authors.lastname: Barakat
authors.forename: Nisha
authors.initials: N
authors.lastname: Gupta
authors.forename: Linda
authors.initials: L
authors.lastname: Rose
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pianta
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D000293:Adolescent; D001766:Blindness / Q000151:congenital*; D002648:Child; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008875:Middle Aged; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D010375:Pedigree; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D018807:Polymorphism, Single-Stranded Conformational; D012162:Retinal Degeneration / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: D006162:Guanylate Cyclase