title: Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response.
abstract: Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very rare autosomal recessive retinal disorder. CDSRR is associated with mutations in KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated potassium channel. In this study, we found that KCNV2 mutations are present in a substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR is underdiagnosed and more common than previously thought. In total, we identified 20 different KCNV2 mutations; 15 of them are novel. A new finding of this study is the substantial proportion of large deletions at the KCNV2 locus that accounts for 15.5% of the mutant alleles in our sample. We determined the breakpoints and size of all five different deletions, which ranged between 10.9 and 236.8 kb. Two deletions encompass the entire KCNV2 gene and one also includes the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid substitution mutations for its effect on interaction with Kv2.1 using yeast two-hybrid technology. We found that these mutations dramatically reduce or abolish this interaction suggesting a lack of assembly of heteromeric Kv channels as one underlying pathomechanism of CDSRR.
authors: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University Clinics Tübingen, Germany. wissinger@uni-tuebingen.de
authors: Bernd
authors: B
authors: Wissinger
authors: Simone
authors: S
authors: Schaich
authors: Britta
authors: B
authors: Baumann
authors: Michael
authors: M
authors: Bonin
authors: Herbert
authors: H
authors: Jägle
authors: Christoph
authors: C
authors: Friedburg
authors: Balázs
authors: B
authors: Varsányi
authors: Carel B
authors: CB
authors: Hoyng
authors: Hélène
authors: H
authors: Dollfus
authors: John R
authors: JR
authors: Heckenlively
authors: Thomas
authors: T
authors: Rosenberg
authors: Günter
authors: G
authors: Rudolph
authors: Ulrich
authors: U
authors: Kellner
authors: Roberto
authors: R
authors: Salati
authors: Astrid
authors: A
authors: Plomp
authors: Elfride
authors: E
authors: De Baere
authors: Monika
authors: M
authors: Andrassi-Darida
authors: Alexandra
authors: A
authors: Sauer
authors: Christiane
authors: C
authors: Wolf
authors: Ditta
authors: D
authors: Zobor
authors: Antje
authors: A
authors: Bernd
authors: Bart P
authors: BP
authors: Leroy
authors: Péter
authors: P
authors: Enyedi
authors: Frans P M
authors: FP
authors: Cremers
authors: Birgit
authors: B
authors: Lorenz
authors: Eberhart
authors: E
authors: Zrenner
authors: Susanne
authors: S
authors: Kohl
mesh_terms: D019943:Amino Acid Substitution; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D010375:Pedigree; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D017384:Sequence Deletion; D020798:Two-Hybrid System Techniques
chemical_list: C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated