title: Ocular and extra-ocular features of patients with Leber congenital amaurosis and mutations in CEP290.
abstract: OBJECTIVE
  This study investigated the centrosomal protein, 290-KD (CEP290) associated genotype and ocular and extra-ocular phenotype in 18 patients with Leber congenital amaurosis (LCA).
  
  
  METHODS
  Eighteen patients with LCA from 14 families with mutations in the CEP290 gene were identified with sequencing or with heteroduplex analysis. Ophthalmic examinations were performed on all patients. Scans of the central nervous system were reassessed in three patients and obtained in two. Renal function was evaluated in all patients. Ultrasonography of the kidneys was performed in six patients.
  
  
  RESULTS
  Eight patients (from five families) carried the c.2991+1655A>G mutation homozygously. Nine solitary patients carried this variant combined with a nonsense, frameshift, or splice site mutation on the second allele. One new nonsense mutation was identified: c.1078C>T. Fourteen patients (from 12 families) had been completely blind from birth or had light perception. The best-recorded visual acuity was 20/200. Peripheral fundus changes appeared to be progressive with a relatively preserved posterior pole. Novel ophthalmic features for the CEP290 phenotype were Coats-like exudative vasculopathy in two patients, a small chorioretinal coloboma in one patient, and well defined, small, atrophic spots at the level of the retinal pigment epithelium causing a dot-like appearance in five patients. Some CEP290 patients exhibited systemic abnormalities. We found abnormal proprioception in two patients and mild mental retardation in one. One patient was infertile due to immobile spermatozoa. No renal abnormalities were detected.
  
  
  CONCLUSIONS
  CEP290-associated LCA has a severe, progressive, and clinically identifiable phenotype. Distinct extra-ocular findings were noted, which may be attributed to ciliary dysfunction.
authors.affiliation: The Rotterdam Eye Hospital, Rotterdam, The Netherlands. yzer@eyehospital.nl
authors.forename: Suzanne
authors.initials: S
authors.lastname: Yzer
authors.forename: Anneke I den
authors.initials: AI
authors.lastname: Hollander
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Jan-Willem R
authors.initials: JW
authors.lastname: Pott
authors.forename: Jan Tjeerd H N
authors.initials: JT
authors.lastname: de Faber
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
mesh_terms: D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005123:Eye / Q000473:pathology; D005260:Female; D005451:Fluorescein Angiography; D056726:Genetic Association Studies; D006801:Humans; D007248:Infertility, Male / Q000235:genetics; D057130:Leber Congenital Amaurosis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins