title: Dominant Retinitis Pigmentosa, p.Gly56Arg Mutation in NR2E3: Phenotype in a Large Cohort of 24 Cases.
abstract: OBJECTIVE
  This research is the single largest NR2E3 genotype-phenotype correlation study performed to date in autosomal dominant Retinitis Pigmentosa.
  
  
  OBJECTIVE
  The aim of this study is to analyse the frequency of the p.Gly56Arg mutation in NR2E3 for the largest cohort of autosomal dominant Retinitis Pigmentosa patients to date and its associated phenotype.
  
  
  METHODS
  A cohort of 201 unrelated Spanish families affected by autosomal dominant Retinitis Pigmentosa. The p.Gly56Arg mutation in the NR2E3 (NM_014249.2) gene was analysed in 201 families. In the 24 cases where the mutation had been detected, a haplotype analysis linked to the p.Gly56Arg families was performed, using four extragenic polymorphic markers D15S967, D15S1050, D15S204 and D15S188. Phenotype study included presence and age of onset of night blindness, visual field loss and cataracts; and an ophthalmoscopic examination after pupillary dilation and electroretinogram for the 24 cases.
  
  
  RESULTS
  Seven of the 201 analyzed families were positive for the p.Gly56Arg, leading to a prevalence of 3.5%. Clinical data were available for 24 subjects. Night blindness was the first noticeable symptom (mean 15.9 years). Visual field loss onset was variable (23.3 ± 11.9 years). Loss of visual acuity appeared late in the disease´s evolution. Most of the patients with cataracts (50%) presented it from the third decade of life. Fundus changes showed inter and intrafamiliar variability, but most of the patients showed typical RP changes and it was common to find macular affectation (47.4%). Electroretinogram was impaired from the beginning of the disease. Two families shared a common haplotype. Additionally, all patients shared a 104Kb region between D15S1050 and the NR2E3 gene.
  
  
  CONCLUSIONS
  This study highlights the importance of p.Gly56Arg in the NR2E3 gene as a common mutation associated with adRP, and provides new clues to its phenotype, which can allow for a better clinical management and genetic counselling of patients and their families.
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Fiona
authors.initials: F
authors.lastname: Blanco-Kelly
authors.affiliation: Instituto de Medicina Genómica (IMEGEN), Valencia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García Hoyos
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Lopez Martinez
authors.affiliation: Department of Ophthalmology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Madrid, Spain.
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Lopez-Molina
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Riveiro-Alvarez
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernandez-San Jose
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Almudena
authors.initials: A
authors.lastname: Avila-Fernandez
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Corton
authors.affiliation: Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.|Grupo de Investigación en Biomedicina Molecular, Celular y Genómica, Instituto de Investigación Sanitaria La Fe (IIS-La Fe), Valencia, Spain.|Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Millan
authors.affiliation: Department of Ophthalmology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital (IIS-FJD, UAM), Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: García Sandoval
authors.affiliation: Genetic´s Department, Instituto de Investigación Sanitaria-Fundación Jimenez Diaz University Hospital (IIS-FJD, UAM), Madrid, Spain.|Center of Biomedical Network Research on Rare Diseases (CIBERER), ISCIII, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004596:Electroretinography; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D009154:Mutation; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010375:Pedigree; D012174:Retinitis Pigmentosa / Q000209:etiology / Q000235:genetics*; D055815:Young Adult
chemical_list: C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors