title: Homozygosity for a Recessive Loss-of-Function Mutation of the NRL Gene Is Associated With a Variant of Enhanced S-Cone Syndrome.
abstract: OBJECTIVE
  To investigate the genetic basis for severe visual complaints by Bukharan Jewish patients with oculopharyngeal muscular dystrophy (OPMD).
  
  
  METHODS
  Polymerase chain reaction amplification and direct sequencing were used to test for NRL, PABPN1, and NR2E3 mutations. Complete ophthalmic examination included best-corrected visual acuity, biomicroscopic examination, optical coherence tomography, and fundus autofluorescence. Detailed electroretinography (ERG) testing was conducted including expanded International Society for Clinical Electrophysiology of Vision protocol for light-adapted and dark-adapted conditions, measurements of S-cone function, and ON-OFF light-adapted ERG.
  
  
  RESULTS
  The index patients were homozygotes for both a dominant mutation of the PABPN1 gene, (GCN)13, and a recessive mutation of the NRL gene, p.R31X, on chromosome 14q11.1, leading to early-onset OPMD accompanied by night blindness and reduced visual acuity. No mutations were found in the NR2E3 gene. Both patients were of Bukharan Jewish origin, but from unrelated families. Electroretinography responses of both patients were dominated by short-wavelength-sensitive mechanisms, with no detectable rod function, similar to the ERG responses of individuals with enhanced S-cone syndrome (ESCS) due to NR2E3 mutations. Heterozygotes for the PABPN1 and NRL mutations demonstrated normal fundi and ERG responses.
  
  
  CONCLUSIONS
  Homozygosity for the recessive NRL mutation described here appears to be associated with a distinct retinal phenotype, demonstrating ERG characteristics similar to those of ESCS patients. This report expands the spectrum of NRL recessive mutations, as well as the genetic spectrum of ESCS, and indicates a new syndrome of OPMD with an ESCS-like phenotype.
authors.affiliation: Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Newman
authors.affiliation: Department of Neurology, Hillel Yaffe Medical Center, Hadera, Israel 4Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Sergiu C
authors.initials: SC
authors.lastname: Blumen
authors.affiliation: Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel 5Unit of Otolaryngology-Head & Neck Surgery, Hillel Yaffe Medical Center, Hadera, Israel.
authors.forename: Itzhak
authors.initials: I
authors.lastname: Braverman
authors.affiliation: Department of Ophthalmology, Hillel Yaffe Medical Center, Hadera, Israel.
authors.forename: Rana
authors.initials: R
authors.lastname: Hanna
authors.affiliation: Department of Ophthalmology, Hillel Yaffe Medical Center, Hadera, Israel.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Tiosano
authors.affiliation: Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel 4Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Ido
authors.initials: I
authors.lastname: Perlman
authors.affiliation: Ruth & Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yosef
mesh_terms: D000293:Adolescent; D000328:Adult; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006720:Homozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D041623:Tomography, Optical Coherence / Q000379:methods; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D014792:Visual Acuity; D055815:Young Adult
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D005136:Eye Proteins; C490037:NRL protein, human; D004247:DNA