title: Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene.
abstract: OBJECTIVE
  To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP).
  
  
  METHODS
  Genomic DNA was isolated from blood samples obtained from 50 patients with Leber Congenital Amaurosis (LCA), 17 patients with the Enhanced S-Cone Syndrome (ESCS), and a patient with an atypical retinal degeneration that causes photoreceptor rosettes with blue cone opsin. The 5' upstream region (putative promoter), untranslated exon 1, coding exons 2 and 3, and exon-intron boundaries of the NRL gene were analyzed by direct sequencing of the PCR-amplified products.
  
  
  RESULTS
  Complete sequencing of the NRL gene in DNA samples from this cohort of patients revealed only one nucleotide change. The C->G transversion at nucleotide 711 of NRL exon 3 was detected in one LCA patient; however, this change did not alter the amino acid (L237L).
  
  
  CONCLUSIONS
  No potential disease causing mutation was identified in the NRL gene in patients with LCA, ESCS, or the atypical retinal degeneration. Together with previous studies, our results demonstrate that mutations in the NRL gene are not a major cause of retinopathy. To date, only missense changes have been reported in adRP patients, and sequence variations are rare. It is possible that the loss of NRL function in humans is associated with a more complex clinical phenotype due to its expression in pineal gland in addition to rod photoreceptors.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA.
authors.forename: Ceren
authors.initials: C
authors.lastname: Acar
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Mears
authors.forename: Beverly M
authors.initials: BM
authors.lastname: Yashar
authors.forename: Anjali S
authors.initials: AS
authors.lastname: Maheshwary
authors.forename: Sten
authors.initials: S
authors.lastname: Andreasson
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.forename: Maria A
authors.initials: MA
authors.lastname: Musarella
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors; D001766:Blindness / Q000151:congenital / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D009154:Mutation; D029242:Optic Atrophy, Hereditary, Leber / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012164:Retinal Diseases / Q000235:genetics* / Q000473:pathology; D017422:Sequence Analysis, DNA; D013577:Syndrome; D014157:Transcription Factors / Q000235:genetics
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005136:Eye Proteins; C490037:NRL protein, human; D014157:Transcription Factors