title: High prevalence of PRPH2 in autosomal dominant retinitis pigmentosa in france and characterization of biochemical and clinical features.
abstract: OBJECTIVE
  To assess the prevalence of PRPH2 in autosomal dominant retinitis pigmentosa (adRP), to report 6 novel mutations, to characterize the biochemical features of a recurrent novel mutation, and to study the clinical features of adRP patients.
  
  
  METHODS
  Retrospective clinical and molecular genetic study.
  
  
  METHODS
  Clinical investigations included visual field testing, fundus examination, high-resolution spectral-domain optical coherence tomography (OCT), fundus autofluorescence imaging, and electroretinogram (ERG) recording. PRPH2 was screened by Sanger sequencing in a cohort of 310 French families with adRP. Peripherin-2 protein was produced in yeast and analyzed by Western blot.
  
  
  RESULTS
  We identified 15 mutations, including 6 novel and 9 previously reported changes in 32 families, accounting for a prevalence of 10.3% in this adRP population. We showed that a new recurrent p.Leu254Gln mutation leads to protein aggregation, suggesting abnormal folding. The clinical severity of the disease in examined patients was moderate with 78% of the eyes having 1-0.5 of visual acuity and 52% of the eyes retaining more than 50% of the visual field. Some patients characteristically showed vitelliform deposits or macular involvement. In some families, pericentral RP or macular dystrophy were found in family members while widespread RP was present in other members of the same families.
  
  
  CONCLUSIONS
  The mutations in PRPH2 account for 10.3% of adRP in the French population, which is higher than previously reported (0%-8%) This makes PRPH2 the second most frequent adRP gene after RHO in our series. PRPH2 mutations cause highly variable phenotypes and moderate forms of adRP, including mild cases, which could be underdiagnosed.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France. Electronic address: gael.manes@inserm.fr.
authors.forename: Gaël
authors.initials: G
authors.lastname: Manes
authors.affiliation: University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Tremeur
authors.initials: T
authors.lastname: Guillaumie
authors.affiliation: The Marie Curie Laboratory for Membrane Proteins, National University of Ireland, Maynooth, Ireland.
authors.forename: Werner L
authors.initials: WL
authors.lastname: Vos
authors.affiliation: CHRU Lille, Laboratoire de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Devos
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM, Direction de l'Hospitalisation et de l'Organisation des Soins, Centre d'Investigation Clinique 1423, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Audo
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France.
authors.forename: Christina
authors.initials: C
authors.lastname: Zeitz
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Marquette
authors.affiliation: Clinique Ophtalmologique Sourdille, Nantes, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Zanlonghi
authors.affiliation: Laboratoire Neurosciences Fonctionnelles et Pathologies, CNRS FRE 2726, Hôpital Roger Salengro, Lille, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Defoort-Dhellemmes
authors.affiliation: Laboratoire Neurosciences Fonctionnelles et Pathologies, CNRS FRE 2726, Hôpital Roger Salengro, Lille, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Puech
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM, Direction de l'Hospitalisation et de l'Organisation des Soins, Centre d'Investigation Clinique 1423, Paris, France.
authors.forename: Saddek Mohand
authors.initials: SM
authors.lastname: Said
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U968, Paris, France; Centre National de la Recherche Scientifique, UMR 7210, Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Paris 06, UMR S968, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, INSERM, Direction de l'Hospitalisation et de l'Organisation des Soins, Centre d'Investigation Clinique 1423, Paris, France.
authors.forename: José Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: Centre Hospitalier Universitaire de Rennes, Rennes, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.affiliation: Hôpitaux Universitaires de Strasbourg (HUS), Centre de référence pour les affections rares en génétique ophtalmologique (CARGO), Strasbourg, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dollfus
authors.affiliation: Department of Genetics, INSERM U781, Hôpital Necker Enfants Malades, Université Paris-Descartes, Paris, France.
authors.forename: Josseline
authors.initials: J
authors.lastname: Kaplan
authors.affiliation: Groupe Hospitalier Necker-Enfants Malades, Université Paris-Descartes, Paris, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Dufier
authors.affiliation: CHU-Hotel Dieu, Service d'Ophtalmologie, Nantes, France.
authors.forename: Guylène
authors.initials: G
authors.lastname: Le Meur
authors.affiliation: CHU-Hotel Dieu, Service d'Ophtalmologie, Nantes, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Weber
authors.affiliation: Centre de génétique, hôpital d'Enfants, université de Dijon, Dijon, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
authors.affiliation: Paris Descartes University, AP-HP Hôtel-Dieu Hospital, Department of Ophthalmology, Paris, France.
authors.forename: Francine Behar
authors.initials: FB
authors.lastname: Cohen
authors.affiliation: INSERM UMR_S 910, University of Aix-Marseille, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.affiliation: Clinical Investigation Centre, University Hospital of Montpellier, Montpellier, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Picot
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Verdier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sénéchal
authors.affiliation: University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Baudoin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Bocquet
authors.affiliation: The Marie Curie Laboratory for Membrane Proteins, National University of Ireland, Maynooth, Ireland.
authors.forename: John B
authors.initials: JB
authors.lastname: Findlay
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Meunier
authors.affiliation: CHRU Lille, Laboratoire de Biochimie et Biologie Moléculaire, UF Génopathies, Lille, France; Université Lille Nord de France, Lille, France.
authors.forename: Claire-Marie
authors.initials: CM
authors.lastname: Dhaenens
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1051, Institute for Neurosciences of Montpellier, Montpellier, France; University of Montpellier 1, Montpellier, France; University of Montpellier 2, Montpellier, France; CHRU, Genetics of Sensory Diseases, Montpellier, France.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Hamel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005602:France / Q000453:epidemiology; D015870:Gene Expression; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D008967:Molecular Biology; D009154:Mutation; D010375:Pedigree; D064531:Peripherins / Q000235:genetics*; D015995:Prevalence; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D058609:Visual Field Tests
chemical_list: C578997:PRPH2 protein, human; D064531:Peripherins