Large deletions of the KCNV2 gene are common in patients with cone dystrophy with supernormal rod response
| Autor: | Ulrich Kellner, Bernd Wissinger, Eberhart Zrenner, Hélène Dollfus, Balázs Varsányi, Günter Rudolph, Susanne Kohl, Britta Baumann, John R. Heckenlively, Elfride De Baere, Thomas Rosenberg, Frans P.M. Cremers, Monika Andrassi-Darida, Christiane Wolf, Ditta Zobor, Simone Schaich, Astrid S. Plomp, Roberto Salati, Carel B. Hoyng, Péter Enyedi, Birgit Lorenz, Antje Bernd, Christoph Friedburg, Alexandra Sauer, Michael Bonin, Bart P. Leroy, Herbert Jägle |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN), Human Genetics, Paediatric Genetics |
| Rok vydání: | 2011 |
| Předmět: |
Genetics
Heterozygote Genetics and epigenetic pathways of disease [NCMLS 6] Cone dystrophy with supernormal rod response Protein subunit Mutant Breakpoint Homozygote Locus (genetics) Biology Pedigree Amino Acid Substitution Potassium Channels Voltage-Gated Two-Hybrid System Techniques Evaluation of complex medical interventions Genomic disorders and inherited multi-system disorders [NCEBP 2] Humans Allele Gene Genetics (clinical) VLDLR Gene Retinitis Pigmentosa Sequence Deletion |
| Zdroj: | Human Mutation, 32, 1398-406 Human Mutation, 32, 12, pp. 1398-406 Human Mutation, 32, 1398-1406. Wiley-Liss Inc. Human mutation, 32(12), 1398-1406. Wiley-Liss Inc. |
| ISSN: | 1059-7794 |
| Popis: | Item does not contain fulltext 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. 32:1398-1406, 2011. (c)2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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