title: Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2.
abstract: OBJECTIVE
  Cone dystrophy with supernormal rod response (CDSRR) is a retinal disorder characterized by reduced visual acuity, color vision defects, and specific alterations of ERG responses that feature elevated scotopic b-wave amplitudes at high luminance intensities. Mutations in PDE6H and in KCNV2 have been described in CDSRR. A combined clinical and genetic study was conducted in a cohort of patients with CDSRR, to substantiate these prior
  
  
  RESULTS
  
  
  
  METHODS
  Seventeen patients from 13 families underwent a detailed ophthalmic examination including color vision testing, Goldmann visual fields, fundus photography, Ganzfeld and multifocal ERGs, and optical coherence tomography. The coding sequences and flanking intron/UTR sequences of PDE6C and KCNV2 were screened for mutations by means of DHPLC and direct DNA sequencing of PCR-amplified genomic DNA. results. Whereas no mutations were detected in the PDE6H gene, mutations in KCNV2 were identified in all patients, in either the homozygous or compound heterozygous state. Ten of the 11 identified mutations were novel, including three missense and six truncating mutations and one gross deletion. The mutations concordantly segregate in all available families according a recessive mode of inheritance. The CDSRR phenotype was associated with reduced visual acuity of variable degree and color vision defects. Macular defects ranging from mild pigmentary changes to distinct foveal atrophy were present in nine patients. Progression of the disease was observed in only three of seven patients with follow-up data.
  
  
  CONCLUSIONS
  The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2.
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University Clinics Tübingen, Germany. wissinger@uni-tuebingen.de
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Susann
authors.initials: S
authors.lastname: Dangel
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Britta
authors.initials: B
authors.lastname: Baumann
authors.forename: Günther
authors.initials: G
authors.lastname: Rudolph
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.forename: Michael
authors.initials: M
authors.lastname: Bonin
authors.forename: Katja
authors.initials: K
authors.lastname: Koeppen
authors.forename: Thomas
authors.initials: T
authors.lastname: Ladewig
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D003119:Color Perception Tests; D003117:Color Vision Defects / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D017948:Retinal Rod Photoreceptor Cells / Q000503:physiopathology*; D041623:Tomography, Optical Coherence; D014794:Visual Fields
chemical_list: D005136:Eye Proteins; C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C096885:PDE6C protein, human