title: Clinical Characterization of CNGB1-Related Autosomal Recessive Retinitis Pigmentosa.
abstract: OBJECTIVE
  There are limited published data on the phenotype of retinitis pigmentosa (RP) related to CNGB1 variants. These data are needed both for prognostic counseling of patients and for understanding potential treatment windows.
  
  
  OBJECTIVE
  To describe the detailed clinical and molecular genetic findings in a series of patients with RP with likely pathogenic variants in CNGB1.
  
  
  METHODS
  In this case series, 10 patients from 9 families underwent full ophthalmologic examination. Molecular investigations included whole-exome analysis in 6 patients. The study was conducted from April 17, 2013, to March 3, 2016, with final follow-up completed on March 2, 2016, and data were analyzed from October 27, 2014, to March 29, 2016.
  
  
  METHODS
  Results of ophthalmologic examination and molecular genetic analysis of CNGB1.
  
  
  RESULTS
  In this case series, 7 women and 3 men from 9 families with a mean (SD) age of 47.4 (13.2) years identified as having CNGB1 variants were included in this study; there was a mean (SD) follow-up length of 3.7 (2.8) years. The first clinical presentation was with nyctalopia in childhood with visual field loss documented later at a mean (SD) age of 33.2 (8.0) years. All patients had preserved best-corrected visual acuity into adulthood, with a mean of 0.1 logMAR (Snellen equivalent, 20/25) in each eye (logMAR range, 0.0 to 0.3 [Snellen 20/20 to 20/40] in the right eye and -0.1 to 0.3 [Snellen 20/16 to 20/40] in the left eye). Fundus examination revealed midperipheral retinal pigment epithelial atrophy and intraretinal pigment migration. Optical coherence tomography of the macula demonstrated complete preservation of the inner segment ellipsoid band in 1 patient, with variable lateral extent in the other patients corresponding to the diameter of a paracentral ring of increased fundus autofluorescence. Electrophysiologic testing in 6 patients confirmed a rod-cone dystrophy phenotype. Molecular investigations identified a previously reported missense variant (p.[N986I]) and 7 variants not previously reported in disease including 4 nonsense (p.[(Q88*], p.[Q222*], p.[Q318*], and p.[R729*]), 2 frameshift (p.[A1048fs*13], p.[L849Afs*3]), and a splice site variant (c.761 + 2T>A).
  
  
  CONCLUSIONS
  The data from this study suggest that visual acuity and foveal structure in patients with RP are preserved into adult life such that a lengthy window of opportunity should exist for intervention with novel therapies.
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hull
authors.affiliation: Moorfields Eye Hospital, London, England3L'Unità Operativa di Oculistica, Ospedale Sacrocuore-Don Calabria, Negrar, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Attanasio
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: Department of Haematology, University of Cambridge, Cambridge, England5National Institute for Health Research (NIHR) BioResource-Rare Diseases, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, England.
authors.forename: Keren
authors.initials: K
authors.lastname: Carss
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Robson
authors.affiliation: Department of Ophthalmology, Great Ormond Street Hospital for Children, London, England.
authors.forename: Dorothy A
authors.initials: DA
authors.lastname: Thompson
authors.affiliation: University College London Genetics Institute, London, England.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: Moorfields Eye Hospital, London, England6Department of Ophthalmology, Great Ormond Street Hospital for Children, London, England.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Henderson
authors.affiliation: National Institute for Health Research (NIHR) BioResource-Rare Diseases, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, England8Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, England.
authors.forename: F Lucy
authors.initials: FL
authors.lastname: Raymond
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England9Ophthalmology Department, University of California, San Francisco Medical School, San Francisco.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: Moorfields Eye Hospital, London, England2University College London Institute of Ophthalmology, London, England.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster