title: Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.
abstract: OBJECTIVE
  To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.
  
  
  METHODS
  Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing.
  
  
  RESULTS
  All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of
  
  
  METHODS
  in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found.
  
  
  CONCLUSIONS
  New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.
authors.affiliation: Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Ophthalmic Research Institute, Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: Booij
authors.forename: R J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: J B
authors.initials: JB
authors.lastname: ten Brink
authors.forename: W
authors.initials: W
authors.lastname: Loves
authors.forename: F
authors.initials: F
authors.lastname: Meire
authors.forename: M J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: P T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: A A B
authors.initials: AA
authors.lastname: Bergen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011956:Receptors, Cell Surface; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C403625:AIPL1 protein, human; C448939:CRB1 protein, human; C415903:RPGRIP1 protein, human; C110715:guanylate cyclase 1