title: Novel RPE65 mutations associated with Leber congenital amaurosis in Chinese patients.
abstract: OBJECTIVE
  Retinal pigment epithelium-specific protein 65 kDa (RPE65) plays an essential role in vitamin A metabolism necessary for synthesizing the visual pigment 11-cis-retinal chromophore. Mutations in RPE65 cause the childhood blindness disorder known as Leber congenital amaurosis (LCA), as well as autosomal recessive retinitis pigmentosa (RP). The purpose of this study was to identify RPE65 mutations in Chinese patients with LCA, determine the prevalence of RPE65 mutations in this cohort, and assess the clinical features of those patients with RPE65 mutations.
  
  
  METHODS
  Detailed ocular examinations were performed, and genomic DNA was isolated with standard methods for genetic diagnosis. All 14 exons of RPE65 were amplified with PCR and screened for mutation with direct DNA sequencing. Two hundred unrelated healthy Chinese subjects were screened to exclude nonpathogenic polymorphisms. Multiple alignments of eight eukaryotic RPE65 orthologs were performed.
  
  
  RESULTS
  A total of 101 LCA patients, drawn from 100 unrelated families, were selected for mutation screening in the RPE65 gene. Compound heterozygous missense mutations Leu67Arg and Tyr368Cys were identified in two affected sisters and segregated with their family. Four previously reported polymorphisms were identified in this study. No other disease-related mutation was detected. The frequency spectrum of variations in the RPE65 gene was estimated to be 1% (1/100) in this cohort of Chinese patients with LCA. The two patients showed classical signs of LCA with relatively preserved central vision and retinal structure.
  
  
  CONCLUSIONS
  The RPE65 mutation is a rare cause of LCA in the Chinese population. Compound heterozygous missense mutations Leu67Arg and Tyr368Cys are related to a relatively mild LCA phenotype. Genetic characterization of patients with RPE65 mutations is important for future rational therapies.
authors.affiliation: Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Dong
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Liang
authors.forename: Ruxin
authors.initials: R
authors.lastname: Jiang
authors.forename: Ruifang
authors.initials: R
authors.lastname: Sui
authors.forename: Fangtian
authors.initials: F
authors.lastname: Dong
mesh_terms: D000293:Adolescent; D000818:Animals; D044466:Asian People; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D019745:cis-trans-Isomerases / Q000235:genetics*; D000099178:Retinoid Isomerohydrolase
chemical_list: D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase