title: Analysis of three genes in Leber congenital amaurosis in Indonesian patients.
abstract: OBJECTIVE
  To assess the frequency, the pattern of disease causing mutations, and phenotypic variations in patients with Leber congenital amaurosis (LCA) from Indonesia.
  
  
  METHODS
  Twenty-one unrelated index cases with a clinical diagnosis of LCA were screened for mutations in the coding sequence of RetGC1, RPE65 and AIPL1 gene with single strand conformation polymorphism analysis followed by direct sequencing and restriction enzyme digestion.
  
  
  RESULTS
  Four novel disease causing mutations were identified: Three in the RPE65 gene (106del9bp, G32V and Y435C) in two of 21 index cases and one in the AIPL1 (K14E). Two of them were homozygous and one was compound-heterozygous. No disease causing mutation was identified in RetGC1.
  
  
  CONCLUSIONS
  The four novel disease causing mutations identified in this study confirmed the diagnosis of LCA which has not been recognized before in Indonesia. The frequency of RPE65 mutations was 9.5%; and of AIPL1 mutations 4.8%. This was in general accordance with previous studies reported from other countries. Unlike in those studies, no disease causing RetGC1 mutations could be identified in our patients. Phenotypically, the RPE65 and AIPL1 mutations identified in this study caused nearly total blindness by the second decade of life, but had a different onset of symptoms. The patients with the RPE65 mutations retained some useful visual function until the end of the first decade, which progressed to total blindness during the second decade of life, whereas the (homozygous) AIPL1 mutation was associated with nearly total blindness from infancy on. Therefore, RPE65 mutations have to be considered to cause early onset severe retinal degeneration (EOSRD), and AIPL1 mutations a form of LCA.
authors: Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics, Klinikum, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. ritass@hotmail.com
authors: Rita S
authors: RS
authors: Sitorus
authors: Birgit
authors: B
authors: Lorenz
authors: Markus N
authors: MN
authors: Preising
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D001766:Blindness / Q000151:congenital / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D005136:Eye Proteins; D005260:Female; D005838:Genotype; D006162:Guanylate Cyclase / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007214:Indonesia; D008297:Male; D009154:Mutation / Q000235:genetics*; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005136:Eye Proteins; D006162:Guanylate Cyclase; D011506:Proteins; D011956:Receptors, Cell Surface; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C403625:AIPL1 protein, human; C110715:guanylate cyclase 1