title: Leber congenital amaurosis: first genotyped Hungarian patients and report of 2 novel mutations in the CRB1 and CEP290 genes.
abstract: OBJECTIVE
  To introduce the first Hungarian patients with genetically defined Leber congenital amaurosis (LCA) and to report 2 novel mutations.
  
  
  METHODS
  Seven otherwise healthy patients (4-29 years, 5 male and 2 female) who had an onset of severe visual impairment before age 2 years were investigated. The diagnosis was established in all individuals by medical history, funduscopy, and full-field electroretinogram (ERG). Ocular examination included visual acuity testing, digital fundus photography, and in 6 patients retinal imaging with optical coherence tomography (OCT). Arrayed primer extension microarray screening was performed in all probands. In 2 patients, further Sanger sequencing and targeted next-generation sequencing revealed the second disease allele.
  
  
  RESULTS
  A cone-rod type LCA was revealed in 4 patients and a rod-cone type disease in 3 patients. Five patients presented with maculopathy. Optical coherence tomography (OCT) imaging showed diffuse retinal thickening in 3 probands with severe macular atrophy in one. Full-field ERGs were undetectable or residual in all patients. Genetic screening revealed AIPL1, CRB1, and CEP290 gene-related pathology in 6 patients; in 1 proband, no mutation was found. Three homozygous and 3 compound heterozygous mutations were identified. Two novel variants were detected: c.2536G&gt;T (p.G846X) in the CRB1 gene and c.4929delA (p.Lys1643fsX2) in the CEP290 gene.
  
  
  CONCLUSIONS
  Genetic subtypes identified are among the most common ones in LCA; the phenotypes are consistent with those reported previously. Both novel mutations are predicted to result in a premature translation termination. The phenotype related to the novel CRB1 mutation results in severe atrophic maculopathy.
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Vámos
authors.affiliation: Asper Biotech Ltd, Tartu - Estonia.
authors.forename: Maigi
authors.initials: M
authors.lastname: Külm
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Szabó
authors.affiliation: Asper Biotech Ltd, Tartu - Estonia.
authors.forename: Aune
authors.initials: A
authors.lastname: Ahman
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Lesch
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.|Department of Ophthalmology, University of Pécs Medical School, Pécs - Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Varsányi
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Zoltán Zsolt
authors.initials: ZZ
authors.lastname: Nagy
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: János
authors.initials: J
authors.lastname: Németh
authors.affiliation: Department of Ophthalmology, Faculty of Medicine, Semmelweis University, Budapest - Hungary.
authors.forename: Ágnes
authors.initials: Á
authors.lastname: Farkas
mesh_terms: D000328:Adult; D000951:Antigens, Neoplasm / Q000235:genetics*; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006814:Hungary; D057130:Leber Congenital Amaurosis / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D041623:Tomography, Optical Coherence
chemical_list: D000951:Antigens, Neoplasm; C448939:CRB1 protein, human; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins