title: Long-term follow-up of the human phenotype in three siblings with cone dystrophy associated with a homozygous p.G461R mutation of KCNV2.
abstract: OBJECTIVE
  To provide an up to 14-year overview of the early ocular phenotype in siblings with a homozygous p.G461R mutation in the KCNV2 gene.
  
  
  METHODS
  Two brothers and their sister were followed-up clinically from ages 5 years, 4 years, and 2 months, respectively, including complete ophthalmological examinations. Goldmann visual fields, two-color-threshold (2CT) perimetry, color vision testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), and Ganzfeld electroretinograms (ERGs) were performed according to age-related capabilities. Genetic analyses included whole genome linkage analysis, homozygosity mapping, and candidate gene sequencing.
  
  
  RESULTS
  All three siblings were homozygous for the p.G461R mutation. At 5 months, the younger brother had no nystagmus and Teller-acuity of 3.2 cyc/deg. At older age, all three presented nystagmus, increased light sensitivity, reduced color discrimination, and relative central scotomas. Visual acuities ranged from 20/200 to 20/70. The macula developed minor irregularities of the RPE, thinning in optical coherence tomography, and a ring of increased FAF. Scotopic (rod) sensitivity was reduced by 2 log and photopic sensitivity by 1 log in two-color-threshold perimetry. ERG responses were markedly delayed. Photopic amplitudes were severely reduced. Scotopic b-waves rose steeply with flash intensity, but for the standard flash supernormal amplitudes were only reached in the girl.
  
  
  CONCLUSIONS
  FAF was similar to that in cone-rod dystrophy. Although cone dysfunction was accompanied by rod dysfunction, and scotopic ERGs in patient 2 deteriorated, no patient demonstrated any unequivocal sign of rod degeneration. Grossly delayed b-waves with a steep response-versus-intensity relationship rather than supernormal amplitudes should remind clinicians of this specific condition.
authors.affiliation: Department of Ophthalmology, Justus-Liebig-University, Giessen, Germany. christoph.friedburg@augen.med.uni-giessen.de
authors.forename: Christoph
authors.initials: C
authors.lastname: Friedburg
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Maria
authors.initials: M
authors.lastname: Schambeck
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Birgit
authors.initials: B
authors.lastname: Lorenz
mesh_terms: D002675:Child, Preschool; D003117:Color Vision Defects / Q000235:genetics / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D008040:Genetic Linkage; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D058499:Retinal Dystrophies / Q000235:genetics* / Q000473:pathology*; D035781:Siblings
chemical_list: C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated