Cone dystrophy with supernormal rod response is strictly associated with mutations in KCNV2.
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.
Wissinger
Bernd
B
Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University Clinics Tübingen, Germany. wissinger@uni-tuebingen.de
Dangel
Susann
S
Jägle
Herbert
H
Hansen
Lars
L
Baumann
Britta
B
Rudolph
Günther
G
Wolf
Christiane
C
Bonin
Michael
M
Koeppen
Katja
K
Ladewig
Thomas
T
Kohl
Susanne
S
Zrenner
Eberhart
E
Rosenberg
Thomas
T
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
D005136:Eye Proteins; C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C096885:PDE6C protein, human