title: IMPG2-associated retinitis pigmentosa displays relatively early macular involvement.
abstract: OBJECTIVE
  To provide the first detailed clinical description in patients with RP caused by recessive mutations in IMPG2.
  
  
  METHODS
  This international collaborative study includes 17 RP patients with inherited retinal disease caused by mutations in IMPG2. The patients were clinically (re-)examined, including extensive medical history taking, slit-lamp biomicroscopy, ophthalmoscopy, perimetry, ERG, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, fundus photography, and color vision tests. The main outcome measures included mean age at onset, initial symptom, best-corrected visual acuity, fundus appearance, perimetry results, ERG responses, OCT images, FAF imaging, color vision test reports and DNA sequence variants.
  
  
  RESULTS
  The mean age at onset was 10.5 years (range, 4-20 years). Initial symptoms included night blindness in 59% of patients, a decreased visual acuity in 35%, and visual field loss in 6%. Fundus abnormalities were typical of RP: optic disc pallor, attenuated vessels, bone spicules, and generalized atrophy of the retina and choriocapillaris. Additionally, we observed macular abnormalities in all patients, ranging from subtle mottling of the macular pigment epithelium (two patients) and a bull's eye maculopathy (seven patients) to macular chorioretinal atrophy (seven patients).
  
  
  CONCLUSIONS
  Mutations in IMPG2 cause a severe form of RP with symptoms manifesting in the first 2 decades of life. IMPG2-associated RP is frequently accompanied by macular involvement, ranging from mild pigment alterations to profound chorioretinal atrophy. The resulting decrease in central vision in combination with the severe tunnel vision leads to severe visual impairment in patients with IMPG2-associated RP.
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Ramon A C
authors.initials: RA
authors.lastname: van Huet
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Rob W J
authors.initials: RW
authors.lastname: Collin
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Siemiatkowska
authors.affiliation: Erasmus University Rotterdam Medical Center, Rotterdam, The Netherlands.
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.affiliation: Department of Ophthalmology, Seconda Università degli Studi di Napoli, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Simonelli
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan.
authors.forename: Muhammad I
authors.initials: MI
authors.lastname: Khan
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan Shifa College of Medicine, Islamabad, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.affiliation: Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Thomas
authors.initials: T
authors.lastname: Theelen
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.affiliation: The Rotterdam Eye Hospital, Rotterdam, The Netherlands.
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.affiliation: Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D003119:Color Perception Tests; D003317:Corneal Dystrophies, Hereditary / Q000175:diagnosis / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics; D009887:Ophthalmoscopy; D010375:Pedigree; D011509:Proteoglycans / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics; D014792:Visual Acuity / Q000502:physiology; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology; D055815:Young Adult
chemical_list: C412522:IMPG2 protein, human; D011509:Proteoglycans
keywords: IMPG2; Retinitis pigmentosa; bull's eye maculopathy; macular atrophy; natural course