title: Clinical Characteristics, Mutation Spectrum, and Prevalence of Åland Eye Disease/Incomplete Congenital Stationary Night Blindness in Denmark.
abstract: To assess clinical characteristics, foveal structure, mutation spectrum, and prevalence rate of Åland eye disease (AED)/incomplete congenital stationary night blindness (iCSNB).
  
  
  
  A retrospective survey included individuals diagnosed with AED at a national low-vision center from 1980 to 2014. A subset of affected males underwent ophthalmologic examinations including psychophysical tests, full-field electroretinography, and spectral-domain optical coherence tomography.
  
  
  
  Over the 34-year period, 74 individuals from 35 families were diagnosed with AED. Sixty individuals from 29 families participated in a follow-up study of whom 59 harbored a CACNA1F mutation and 1 harbored a CABP4 mutation. Among the subjects with a CACNA1F mutation, subnormal visual acuity was present in all, nystagmus was present in 63%, and foveal hypoplasia was observed in 25/43 subjects. Foveal pit volume was significantly reduced as compared to normal (P < 0.0001). Additionally, outer segment length at the fovea was measured in 46 subjects and found to be significantly reduced as compared to normal (P < 0.001). Twenty-nine CACNA1F variations were detected among 34 families in the total cohort, and a novel CABP4 variation was identified in one family. The estimated mean birth prevalence rate was 1 per 22,000 live-born males.
  
  
  
  Our data support the viewpoint that AED, iCSNB, and X-linked cone-rod dystrophy 3 are designations that refer to a broad, continuous spectrum of clinical appearances caused in the majority by a variety of mutations in CACNA1F. We argue that the original designation AED should be used for this entity.
authors.affiliation: Department of Ophthalmology, National Eye Clinic for the Visually Impaired and Kennedy Center, Rigshospitalet, Glostrup, Denmark 2Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark.
authors.forename: Marianne N
authors.initials: MN
authors.lastname: Hove
authors.affiliation: Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark 3Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kevser Z
authors.initials: KZ
authors.lastname: Kilic-Biyik
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Alana
authors.initials: A
authors.lastname: Trotter
authors.affiliation: Clinical Genetic Clinic, Kennedy Center, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Grønskov
authors.affiliation: Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark 3Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Birgit
authors.initials: B
authors.lastname: Sander
authors.affiliation: Department of Ophthalmology, National Eye Clinic for the Visually Impaired and Kennedy Center, Rigshospitalet, Glostrup, Denmark 2Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark 3Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Larsen
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Carroll
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Torben
authors.initials: T
authors.lastname: Bech-Hansen
authors.affiliation: Department of Ophthalmology, National Eye Clinic for the Visually Impaired and Kennedy Center, Rigshospitalet, Glostrup, Denmark 3Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D020746:Calcium Channels, L-Type / Q000235:genetics* / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005500:Follow-Up Studies; D005544:Forecasting; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009216:Myopia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D009755:Night Blindness / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015995:Prevalence; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C514441:CABP4 protein, human; C113330:CACNA1F protein, human; D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D004247:DNA